Tryptamine compositions for enhancing neurite outgrowth

ABSTRACT

Described herein are neurotrophic and nootropic compositions and methods for treating subjects with such compositions. In one aspect the composition comprises one or more tryptamines or in pure form or extracts from psilocybin containing mushrooms, or combinations thereof optionally combined with one or more phenethylamines or amphetamines in pure form or extracts from a plant or mushroom, or combinations thereof, optionally one or more erinacines or hericenones in pure form, extracts from  Hericium  mushroom species (e.g.,  H. erinaceus, H. coralloides, H. ramosum ) or combinations thereof, optionally one or more cannabinoids in pure form or extracts from  Cannabis sativa, Cannabis sativa, Cannabis indica , or  Cannabis ruderalis , optionally, one or more adversive compounds, and optionally one or more pharmaceutically acceptable excipients.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.16/951,009, filed Nov. 18, 2020, which claims priority to U.S.Provisional Patent Application No. 62/937,536, filed on Nov. 19, 2019,and U.S. Provisional No. 63/007,482, filed Apr. 9, 2020, each of whichare incorporated by reference herein in its entirety.

TECHNICAL FIELD

Described herein are neurotrophic and nootropic compositions and methodsfor treating subjects with such compositions. In one aspect thecomposition comprises one or more tryptamines or in pure form orextracts from psilocybin containing mushrooms, or combinations thereofoptionally combined with one or more phenethylamines or amphetamines inpure form or extracts from a plant or mushroom, or combinations thereof,optionally one or more erinacines or hericenones in pure form, extractsfrom Hericium mushroom species (e.g., H. erinaceus, H. coralloides, H.ramosum) or combinations thereof, optionally one or more cannabinoids inpure form or extracts from Cannabis sativa, Cannabis sativa, Cannabisindica, or Cannabis ruderalis, optionally, one or more adversivecompounds, and optionally one or more pharmaceutically acceptableexcipients.

BACKGROUND

Serotonin (5-hydroxytryptamine, 5-HT) plays a significant role ininfluencing many central and peripheral processes. 5-HT-selectivepharmacotherapies have been developed to treat a wide variety of medicalproblems including depression, anxiety, schizophrenia, migraine, emesis,and appetite control. 5-HT exerts its influence through activation offourteen distinct receptor subtypes in seven separate families. There isinterest in the three receptor subtypes of the 5-HT₂ family, 5-HT_(2A),5-HT_(2B), and 5-HT_(2C). Modulation of the 5-HT_(2C) receptor subtypehas been shown to play a role in numerous human diseases includingobesity, obsessive-compulsive disorder (OCD), sexual dysfunction,epilepsy, schizophrenia, anxiety disorders, among a variety of otherpsychiatric disorders.

Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) is an agonist at the5-HT₂ and 5-HT_(2C) receptors. Psilocybin's binding potency at 5-HT_(2A)correlates with its activity as a hallucinogen in humans. More than 40years ago, derivatives of psilocybin were reported by workers at Sandoz.See Hofmann and Troxler, U.S. Pat. Nos. 3,075,992; 3,078,214. Recentstudies have shown that psilocybin has neurogenerative properties. SeeCatlow et al., “Effects of psilocybin on hippocampal neurogenesis andextinction of trace fear conditioning,” Expt. Brain Res. 228: 481-491(2013); Phan et al. “Edible and Medicinal Mushrooms: Emerging Brain Foodfor the Mitigation of Neurodegenerative Diseases,” J. Medic. Foods20(1): 1-10 (2017). Schartner et al. reported substantial increasedglobal neural signal diversity in a psilocybin-human clinical study. SeeNature Scientific Reports, 7:46421 (2017). And, Ly et al. showed thatdimethyltryptamine, 2,5-dimethoxy-4-iodoamphetamine (DOI), and LSDpromoted neurogenesis. See Ly et al., “Psychedelics Promote Structuraland Functional Neural Plasticity,” Cell Rep. 23: 3170-3182 (2018).Recent studies have shown that monoamine oxidase (MAO) inhibitorsincrease the pharmacological effects of tryptamines. See Blei et al.,“Simultaneous Production of Psilocybin and a Cocktail of 1-CarbolineMonoamine Oxidase Inhibitors in ‘Magic’ Mushrooms,” Chem. Eur. J. 26(3):729-734 (2020).

Lion's Mane (Hericium erinaceus), Bear's Head (H. coralloides), or CombTooth (H. ramosum) mushrooms and mycelium are reported to influencemyelin regeneration myelin on the axons of nerves. Two cyanthaneterpenes the erinacines and hericenones are thought to promote NGF(nerve growth factor) synthesis. See Friedman, “Chemistry, Nutrition,and Health-Promoting Properties of Hericium erinaceus (Lion's Mane)Mushroom Fruiting Bodies and Mycelia and Their Bioactive Compounds,” J.Agricult. Food Chem. 63: 7108-7123 (2015). Recent studies haveidentified erinacines O and P as inhibitors of gliomas in human U87cells. Zhang et al., “Erinacerins, Novel Glioma Inhibitors from Hericiumerinaceus, Induce Apoptosis of U87 Cells through Bax/Capase-2 Pathway,”Anticancer Agents Med. Chem. Aug. 3, 2020; doi:10.2174/1871520620666200804104243.

The combination of sub-hallucinogenic “microdoses” of tryptamines,phenethylamines, or amphetamines with other neurogenic compounds such asthe erinacines and hericenones, cannabinoids and other neurogenic ornootropic natural products can be used to treat a variety of neuronaldisorders or enchance cognition and sensory motor neuron functioning.There is a need for such neurogenic and nootropic compositions.

SUMMARY

One embodiment described herein is a composition comprising norpsilocinor a salt or hydrate thereof or combinations thereof combined with oneor more erinacines or hericenones in pure form, extracts or isolatesfrom Hericium mushroom species, or combinations thereof. In one aspect,the erinacines or hericenones comprise Erinacine A, Erinacine B,Erinacine C, Erinacine D, Erinacine E, Erinacine F, Erinacine G,Erinacine H, Erinacine I, Erinacine J, Erinacine K, Erinacine O,Erinacine P, Erinacine Q, Erinacine R, Erinacol, other ErinacinesHericenone A, Hericenone B, Hericenone C, Hericenone D, Hericenone E,Hericenone F, Hericenone G, Hericenone H, other hericenones, orpharmaceutically acceptable salts, hydrates, solvates, prodrugs,stereoisomers, or tautomers thereof. In another aspect, the compositioncomprises an extract of extracts or isolates from Hericium erinaceus. Inanother aspect, the composition further comprises baeocystin or a saltor hydrate thereof. In another aspect, the composition comprisesnorbaeocystin and a purified erinacine, hericenone, salts thereof,hydrates thereof, or combination thereof. In another aspect, thecomposition further comprises one or more cannabinoids in pure form orextracts or isolates from Cannabis sativa, Cannabis sativa, Cannabisindica, or Cannabis ruderalis. In another aspect, the cannabinoidscomprise one or more of Δ8-tetrahydrocannabinol (THC),Δ9-tetrahydrocannabinol, tetrahydrocannabinolic acid (THCA), cannabidiol(CBD), cannabidiolic acid (CBDA), cannabinol (CBN), cannabigerol (CBG),cannabichromene (CBC), cannabicyclol (CBL), cannabivarin (CBV),tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabichromevarin(CBCV), cannabigerovarin (CBGV), cannabigerol monomethyl ether (CBGM),cannabielsoin (CBE), cannabicitran (CBT), among others, orpharmaceutically acceptable salts, hydrates, solvates, prodrugs,stereoisomers, or tautomers thereof. In another aspect, the compositionfurther comprises one or more phenethylamines or amphetamines in pureform or extracts or isolates from plants comprising thereof. In anotheraspect, the phenethylamines or amphetamines comprises3,4,5-trimethoxyphenethylamine (Mescaline),2,5-dimethoxy-4-methylamphetamine (DOM),2,5-dimethoxy-4-bromophenethylamine (2C-B),2,5-dimethoxy-4-ethylphenethylamine (2C-E),2,5-dimethoxy-4-ethylthiophenethylamine (2C-T-2),2,5-dimethoxy-4-propylthiophenethylamine (2C-T-7), p-methoxy-amphetamine(PMA), 2,4-dimethoxy-amphetamine (2,4-DMA), 3,4-dimethoxy-amphetamine(3,4-DMA), 3,4-methylenedioxy-amphetamine (MDA),3-methoxy-4,5-methylendioxy-amphetamine (MMDA),2-methoxy-3,4-methylendioxyamphetamine (MMDA-3a),2-methoxy-4,5-methylendioxyamphetamine (MMDA-2),3,4,5-trimethoxyamphetamine (TMA), 2,4,5-trimethoxyamphetamine (TMA-2),2,5-dimethoxy-3,4-methylenedioxyamphetamine (DMMDA),2,3-dimethoxy-4,5-methylenedioxyamphetamine (DMMDA-2),2,3,4,5-tetramethoxyamphetamine (TeMA),(R)-2,5-dimethoxy-4-iodoamphetamine, inter alia, pharmaceuticallyacceptable salts, hydrates, solvates, prodrugs, stereoisomers, ortautomers thereof. In another aspect, the composition further comprisesone or more adversive compounds comprising niacin, ipecac, apomorphine,bittering agents (e.g., denatonium benzoate), capsaicin, capsacutindihydrocapsaicin, nordihydrocapsaicin, homocapsaicin,homodihydrocapsaicin, capsaicinoids, gingerol, pipeline, isopiperine,zingerone, shogaol, vanillylamide derivatives, or combinations thereof.In another aspect, the adversive is niacin. In another aspect, thecomposition comprises an extract of extracts or isolates from Hericiumerinaceus and niacin. In another aspect, the composition comprises anextract of extracts or isolates from Pochonia chlamydosporia. In anotheraspect, the composition comprises ketamine, pharmaceutically acceptablesalts, hydrates, solvates, prodrugs, stereoisomers, or tautomersthereof. In another aspect, the composition comprises 0.001 mg to 0.01mg, 0.01 mg to 0.1 mg, 0.01 mg to 1 mg, 0.1 mg to 5 mg, 0.1 mg to 1 mg,0.5 mg to 1 mg, 0.5 mg to 5 mg, 0.25 mg to 1 mg, 0.2 mg to 2 mg, or 0.2mg to 5 mg of norpsilocin or an amount of a mushroom extract or mushroomto provide an equivalent dose. In another aspect, the compositioncomprises 1 μg to 5 μg, 1 μg to 10 μg, 5 μg to 10 μg, 10 μg to 5 mg, 10μg to 100 μg, 100 μg to 1 mg, 500 μg to 1 mg, 500 μg to 5 mg, 1 mg to 5mg, 100 μg to 1 mg, 100 μg to 500 μg, 100 μg to 250 μg; 250 μg to 1 mg;750 μg to 1 mg, or 250 μg to 750 μg of one or more erinacines orhericenones or an amount of a mushroom extractor mushroom to provide anequivalent dose. In another aspect, the composition comprises 0.01 mg to0.1 mg, 0.01 mg to 1 mg, 0.1 mg to 10 mg, 0.1 mg to 1 mg, 0.5 mg to 1mg, 0.5 mg to 5 mg, 0.25 mg to 1 mg, 0.2 mg to 2 mg, 0.2 mg to 5 mg, or1 mg to 10 mg of one or more cannabinoids or an amount of a plantextract or plant to provide an equivalent dose. In another aspect, thecomposition comprises 0.1 mg to 1 mg, 1 mg to 10 mg, 10 mg to 100 mg, 10mg to 50 mg, 50 mg to 100 mg, 20 mg to 80 mg, 20 mg to 50 mg, 50 mg to100 mg, 50 mg to 80 mg, or 10 mg to 80 mg of one or more phenethylaminesor amphetamines or an amount of a plant or mushroom extract or plant ormushroom to provide an equivalent dose. In another aspect, thecomposition comprises 0.1 mg to 10 mg, 1 mg to 500 mg, 1 mg to 100 mg,200 mg to 500 mg, 50 mg to 200 mg, 10 mg to 50 mg, 50 mg to 200 mg, 1 mgto 200 mg, or 1 mg to 50 mg of one or more adversives. In anotheraspect, the composition comprises one or more pharmaceuticallyacceptable excipients. In another aspect, the composition is a powderadmixture, liquid, suspension, or emulsion. In another aspect, thecomposition further comprises one or more extracts or pure chemicalsfrom other fungi comprising one or more of, Antrodia, Beauvera,Copelandia, Cordyceps, Fomitopsis, Ganoderma, Grifola, Hericium,Hypsizygus, Inonotus, Isaria, Panaeolus, Phellinus, Piptoporus,Pleurotus, Polyporus or Trametes species or combinations thereof; amycelium extract of Antrodia, Beauveria, Copelandia, Cordyceps,Fomitopsis, Ganoderma, Grifola, Hericium, Hypsizygus, Inonotus, Isaria,Panaeolus, Phellinus, Piptoporus, Pleurotus, Polyporus or Trametesspecies or combinations thereof; or a fruiting body extract of Antrodia,Beauveria, Copelandia, Cordyceps, Fomitopsis, Ganoderma, Grifola,Hericium, Hypsizygus, Inonotus, Isaria, Panaeolus, Phellinus,Piptoporus, Pleurotus, Polyporus or Trametes species or combinationsthereof, or combinations thereof. In another aspect, the compositionfurther comprises one or more extracts or pure chemicals from otherplant species comprising Bacopa species (Bacopa monnien), Gotu kola(Centella asiatica), and Gingko (Gingko biloba, Ginger (Zingiberofficinale), Holy Basil (Ocimum sanctum), Hu Zhang (Polygonumcuspidatum), Oregano (Origanum vulgare, Origanum onites), Rosemary(Rosmarinus officinalis, Rosmarinus eriocalyx, species in the genusRosmarinus), Turmeric (Curcuma longa), Green Tea (Camellia sinensis),lavender (Lavandula spica and related species in the genus Lavandula),skullcap (Scutellaria lateriflora) oat straw (Avena sativa, Avenabyzantina), Salvia divinorum, aka Diviner's Sage, Banisteropsis caapiand Psychotria species, plants containing ibogaine (Tabemanthe iboga,Voacanga africana and Tabemaemontana undulate), peyote (Lophophorawilliamsii), the seeds of morning glory (Ipomoea tricolor and relatedspecies) and Hawaiian baby wood rose (Argyreia nervosa), Acacia confusa,Acacia obtusifolia, Acacia simplicifolia, Desmanthus illinoensis, orCannabis (Cannabis sativa, C. indica and C. ruderalis) or combinationsthereof. In another aspect, the composition is effective to treat,alleviate, prevent or ameliorate psychiatric and mood disorderscomprising serotonin (5-hydroxytryptamine, 5-HT) receptor disorders,depression, anxiety, major depressive disorder, treatment resistantdepression, persistent depression, manic depression or bipolar disorder,depressive psychosis, perinatal depression, premenstrual dysphoricdisorder, seasonal depressions, situational depression, panic disorder,obsessive compulsive disorder, post-traumatic stress disorder, attentiondeficit/hyperactivity disorder, sleep disorders, eating disorders,schizophrenia, personality disorders, substance abuse disorders (drugabuse, addiction, alcoholism); neuronal injuries or physicalneurodegeneration (e.g., physical injury, head trauma, spinal cordtrauma, concussion, peripheral neuron trauma, paralysis, ischemia,hypoxia, stroke; organophosphates, lead, heavy metals, nerve agents,other toxic compounds, prions, amyloid plaque, neurotoxic viruses,stress); neurodegenerative diseases (e.g., Alzheimer's disease,Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis,frontotemporal dementia, Huntington's disease, adrenal leukodystrophy,Alexander's disease, Alper's disease, Alzheimer's disease, amyotrophiclateral sclerosis, balo concentric sclerosis, Canavan disease,Charcot-Marie-Tooth disease, childhood ataxia with central nervoussystem hypomyelination, chronic idiopathic peripheral neuropathy,frontotemporal dementia, Huntington's disease, Krabbe disease, monomelicamyotrophy, multiple sclerosis (MS), neurodegeneration, neuromyelitisoptica, neuropathic pain, neurosarcoidosis, Parkinson's disease,Pelizaeus-Merzbacher disease, primary lateral sclerosis, progressivesupranuclear palsy, radicular pain, radiculopathic pain, Schilder'sdisease, sciatic pain, sciatica, subacute necrotizing myelopathy,transverse myelitis, or Zellweger syndrome); congenital or organiccognitive impairment, learning disabilities, autism spectrum disorder;cognitive enhancement, intelligence enhancement, creativity enhancement,memory improvement, learning enhancement and improvement, spiritualenhancement, “mind expansion,” IQ improvement, EQ improvement, balanceenhancement, athleticism, motor skill enhancement, special navigation,clairvoyance, psychic enhancement, or general improvement of mentalhealth.

Another embodiment described herein is a method of treating orpreventing serotonin (5-hydroxytryptamine, 5-HT) receptor disorders,neuronal injuries, neurodegeneration, neurological diseases, congenitalor organic cognitive impairment, learning disabilities, autism spectrumdisorder, psychiatric and mood disorders, cognitive enhancement,physical or motor neuron enhancement, or general improvement of mentalhealth in a subject in need thereof, the method comprising administeringto the subject a therapeutically effective amount of a compositioncomprising one or more tryptamines or in pure form or pharmaceuticallyacceptable salts, hydrates, solvates, prodrugs, stereoisomers, ortautomers thereof, or extracts or isolates from psilocybin containingmushrooms, or combinations thereof combined with one or more erinacinesor hericenones in pure form or pharmaceutically acceptable salts,hydrates, solvates, prodrugs, stereoisomers, or tautomer thereof, orcombinations thereof, extracts or isolates from Hericium mushroomspecies, combinations thereof and one or more pharmaceuticallyacceptable excipients. In one aspect, the composition further comprisesone or more adversive compounds comprising niacin, ipecac, apomorphine,bittering agents (e.g., denatonium benzoate), capsaicin, capsacutindihydrocapsaicin, nordihydrocapsaicin, homocapsaicin,homodihydrocapsaicin, capsaicinoids, gingerol, pipeline, isopiperine,zingerone, shogaol, vanillylamide derivatives, or combinations thereof.

Another embodiment described herein is a method of treating orpreventing serotonin (5-hydroxytryptamine, 5-HT) receptor disorders,neuronal injuries, neurodegeneration, neurological diseases, congenitalor organic cognitive impairment, learning disabilities, autism spectrumdisorder, psychiatric and mood disorders, cognitive enhancement,physical or motor neuron enhancement, or general improvement of mentalhealth in a subject in need thereof, the method comprising administeringto the subject a therapeutically effective amount of a compositioncomprising one or more tryptamines or in pure form or pharmaceuticallyacceptable salts, hydrates, solvates, prodrugs, stereoisomers, tautomersthereof or combinations thereof, or extracts or isolates from psilocybincontaining mushrooms, or combinations thereof combined with one or moreerinacines or hericenones in pure form or pharmaceutically acceptablesalts, hydrates, solvates, prodrugs, stereoisomers, or tautomer thereof,or combinations thereof, extracts or isolates from Hericium mushroomspecies, combinations thereof; one or more cannabinoids in pure form orpharmaceutically acceptable salts, hydrates, solvates, prodrugs,stereoisomers, tautomers thereof, or combinations thereof, or extractsor isolates from Cannabis sativa, Cannabis sativa, Cannabis indica, orCannabis ruderalis; and one or more pharmaceutically acceptableexcipients.

Another embodiment described herein is a method of treating orpreventing serotonin (5-hydroxytryptamine, 5-HT) receptor disorders,neuronal injuries, neurodegeneration, neurological diseases, congenitalor organic cognitive impairment, learning disabilities, autism spectrumdisorder, psychiatric and mood disorders, cognitive enhancement,physical or motor neuron enhancement, or general improvement of mentalhealth in a subject in need thereof, the method comprising administeringto the subject a therapeutically effective amount of a compositioncomprising norpsilocin, norbaeocystin, baeocystin, or psilocybin,combined with one or more erinacines or hericenones in pure form orpharmaceutically acceptable salts, hydrates, solvates, prodrugs,stereoisomers, or tautomer thereof, or combinations thereof, extracts orisolates from Hericium mushroom species, combinations thereof and one ormore pharmaceutically acceptable excipients.

Another embodiment described herein is the use of a pharmaceuticalcomposition comprising one or more tryptamines, erinacines, hericenones,or pharmaceutically acceptable salts, hydrates, solvates, prodrugs,stereoisomers, or tautomers thereof, or combinations thereof and one ormore pharmaceutically acceptable excipients, in the manufacture of amedicament for treatment of serotonin (5-hydroxytryptamine, 5-HT)receptor disorders, neuronal injuries, neurodegeneration, neurologicaldiseases, congenital or organic cognitive impairment, learningdisabilities, autism spectrum disorder, psychiatric and mood disorders,cognitive enhancement, physical or motor neuron enhancement, or generalimprovement of mental health.

Another embodiment described herein is the use of a pharmaceuticalcomposition comprising an effective amount of one or more tryptamines orpharmaceutically acceptable salts, hydrates, solvates, prodrugs,stereoisomers, or tautomers thereof, or combinations thereof and one ormore pharmaceutically acceptable excipients, in the manufacture of amedicament for treating or preventing serotonin (5-hydroxytryptamine,5-HT) receptor disorders, neuronal injuries, neurodegeneration,neurological diseases, congenital or organic cognitive impairment,learning disabilities, autism spectrum disorder, psychiatric and mooddisorders, cognitive enhancement, physical or motor neuron enhancement,or general improvement of mental health.

Another embodiment described herein is the use of a pharmaceuticalcomposition comprising an effective amount of one or more tryptamines,erinacines, hericenones, or pharmaceutically acceptable salts, hydrates,solvates, prodrugs, stereoisomers, or tautomers thereof, or combinationsthereof and one or more pharmaceutically acceptable excipients in themanufacture of a medicament for treating serotonin (5-hydroxytryptamine,5-HT) receptor disorders, neuronal injuries, neurodegeneration,neurological diseases, congenital or organic cognitive impairment,learning disabilities, autism spectrum disorder, psychiatric and mooddisorders, cognitive enhancement, physical or motor neuron enhancement,or general improvement of mental health in a subject in need thereof.

Another embodiment described herein is the use of a pharmaceuticalcomposition comprising an effective amount of one or more tryptamines,erinacines, hericenones, cannabinoids, or pharmaceutically acceptablesalts, hydrates, solvates, prodrugs, stereoisomers, or tautomersthereof, or combinations thereof and one or more pharmaceuticallyacceptable excipients for treating or preventing serotonin(5-hydroxytryptamine, 5-HT) receptor disorders, neuronal injuries,neurodegeneration, neurological diseases, congenital or organiccognitive impairment, learning disabilities, autism spectrum disorder,psychiatric and mood disorders, cognitive enhancement, physical or motorneuron enhancement, or general improvement of mental health in a subjectin need thereof.

Another embodiment described herein is a means for treating orpreventing serotonin (5-hydroxytryptamine, 5-HT) receptor disorders,neuronal injuries, neurodegeneration, neurological diseases, congenitalor organic cognitive impairment, learning disabilities, autism spectrumdisorder, psychiatric and mood disorders, cognitive enhancement,physical or motor neuron enhancement, or general improvement of mentalhealth in a subject in need thereof in in a subject in need thereofcomprising administering a composition comprising an effective amount ofone or more tryptamines, erinacines, hericenones, or pharmaceuticallyacceptable salts, hydrates, solvates, prodrugs, stereoisomers, ortautomers thereof, or combinations thereof and one or morepharmaceutically acceptable excipients to the subject.

Another embodiment described herein is a means for treating orpreventing serotonin (5-hydroxytryptamine, 5-HT) receptor disorders,neuronal injuries, neurodegeneration, neurological diseases, congenitalor organic cognitive impairment, learning disabilities, autism spectrumdisorder, psychiatric and mood disorders, cognitive enhancement,physical or motor neuron enhancement, or general improvement of mentalhealth in a subject in need thereof in in a subject in need thereofcomprising administering a composition comprising an effective amount ofone or more tryptamines, erinacines, hericenones, cannabinoids, orpharmaceutically acceptable salts, hydrates, solvates, prodrugs,stereoisomers, or tautomers thereof, or combinations thereof and one ormore pharmaceutically acceptable excipients to the subject.

Another embodiment described herein is a method for inducing neuritegrowth and neurite lengthening comprising administering an effective aneffective amount of one or more tryptamines or in pure form or extractsor isolates from psilocybin containing mushrooms, or combinationsthereof combined with one or more erinacines or hericenones in pureform, extracts or isolates from Hericium mushroom species, orcombinations thereof and one or more pharmaceutically acceptableexcipients to the subject.

Another embodiment described herein is a method for inducing neuritegrowth and neurite lengthening comprising administering an effective aneffective amount of one or more or norpsilocin, norbaeocystin,baeocystin, or psilocybin combined with one or more erinacines orhericenones in pure form, extracts or isolates from Hericium mushroomspecies, or combinations thereof and one or more pharmaceuticallyacceptable excipients to the subject.

Another embodiment described herein is a process for producing acomposition comprising norpsilocin in pure form or extracts or isolatesfrom psilocybin containing mushrooms, or combinations thereof combinedwith one or more erinacines or hericenones in pure form, extracts orisolates from Hericium mushroom species, or combinations thereof,comprising: growing a mushroom on a substrate; separating mushroommycelium from a fruitbody and the substrate; extracting the mushroommycelium in a solvent, forming a solution; and lyophilizing the extract.In one aspect, the substrate comprises one or more of rice, oat, straw,or sawdust. In another aspect, the solvent is ethanol.

Another embodiment described herein is a composition comprising one ormore tryptamines or in pure form or extracts or isolates from psilocybincontaining mushrooms, or combinations thereof combined with one or moreerinacines or hericenones in pure form, extracts or isolates fromHericium mushroom species, or combinations thereof. In one aspect, thetryptamine comprises, one or more of psilocybin, baeocystin,norbaeocystin, psilocin, norpsilocin, aeruginascin, 4-hydroxytryptamine,N,N-dimethyltryptamine, or N-methyltryptamine; other tryptamines, orpharmaceutically acceptable salts, hydrates, solvates, prodrugs,stereoisomers, or tautomers thereof. In another aspect, the erinacinesor hericenones comprise Erinacine A, Erinacine B, Erinacine C, ErinacineD, Erinacine E, Erinacine F, Erinacine G, Erinacine H, Erinacine I,Erinacine J, Erinacine K, Erinacine P, Erinacine Q, Erinacine R,Erinacol, other Erinacines Hericenone A, Hericenone B, Hericenone C,Hericenone D, Hericenone E, Hericenone F, Hericenone G, Hericenone H,other hericenones, or pharmaceutically acceptable salts, hydrates,solvates, prodrugs, stereoisomers, or tautomers thereof. In anotheraspect, the composition further comprises one or more cannabinoids inpure form or extracts or isolates from Cannabis sativa, Cannabis sativa,Cannabis indica, or Cannabis ruderalis. In another aspect, thecannabinoids comprise one or more of Δ8-tetrahydrocannabinol (THC),Δ9-tetrahydrocannabinol, tetrahydrocannabinolic acid (THCA), cannabidiol(CBD), cannabidiolic acid (CBDA), cannabinol (CBN), cannabigerol (CBG),cannabichromene (CBC), cannabicyclol (CBL), cannabivarin (CBV),tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabichromevarin(CBCV), cannabigerovarin (CBGV), cannabigerol monomethyl ether (CBGM),cannabielsoin (CBE), cannabicitran (CBT), among others, orpharmaceutically acceptable salts, hydrates, solvates, prodrugs,stereoisomers, or tautomers thereof. In another aspect, the compositionfurther comprises one or more phenethylamines or amphetamines in pureform or extracts or isolates from plants comprising thereof. In anotheraspect, the phenethylamines or amphetamines comprises3,4,5-trimethoxyphenethylamine (Mescaline),2,5-dimethoxy-4-methylamphetamine (DOM),2,5-dimethoxy-4-bromophenethylamine (2C-B),2,5-dimethoxy-4-ethylphenethylamine (2C-E),2,5-dimethoxy-4-ethylthiophenethylamine (2C-T-2),2,5-dimethoxy-4-propylthiophenethylamine (2C-T-7), p-methoxy-amphetamine(PMA), 2,4-dimethoxy-amphetamine (2,4-DMA), 3,4-dimethoxy-amphetamine(3,4-DMA), 3,4-methylenedioxy-amphetamine (MDA),3-methoxy-4,5-methylendioxy-amphetamine (MMDA),2-methoxy-3,4-methylendioxyamphetamine (MMDA-3a),2-methoxy-4,5-methylendioxyamphetamine (MMDA-2),3,4,5-trimethoxyamphetamine (TMA), 2,4,5-trimethoxyamphetamine (TMA-2),2,5-dimethoxy-3,4-methylenedioxyamphetamine (DMMDA),2,3-dimethoxy-4,5-methylenedioxyamphetamine (DMMDA-2),2,3,4,5-tetramethoxyamphetamine (TeMA), inter alia, pharmaceuticallyacceptable salts, hydrates, solvates, prodrugs, stereoisomers, ortautomers thereof. In another aspect, the composition further comprisesone or more adversive compounds comprising niacin, ipecac, apomorphine,bittering agents (e.g., denatonium benzoate), capsaicin, capsacutindihydrocapsaicin, nordihydrocapsaicin, homocapsaicin,homodihydrocapsaicin, capsaicinoids, gingerol, pipeline, isopiperine,zingerone, shogaol, vanillylamide derivatives, or combinations thereof.In another aspect, the composition comprises 0.001 mg to 0.01 mg, 0.01mg to 0.1 mg, 0.01 mg to 1 mg, 0.1 mg to 5 mg, 0.1 mg to 1 mg, 0.5 mg to1 mg, 0.5 mg to 5 mg, 0.25 mg to 1 mg, 0.2 mg to 2 mg, or 0.2 mg to 5 mgof one or more tryptamines or an amount of a plant or mushroom extractor plant or mushroom to provide an equivalent dose. In another aspect,the composition comprises 1 μg to 5 μg, 1 μg to 10 μg, 5 μg to 10 μg, 10μg to 5 mg, 10 μg to 100 μg, 100 μg to 1 mg, 500 μg to 1 mg, 500 μg to 5mg, 1 mg to 5 mg, 100 μg to 1 mg, 100 μg to 500 μg, 100 μg to 250 μg;250 μg to 1 mg; 750 μg to 1 mg, or 250 μg to 750 μg of one or moreerinacines or hericenones or an amount of a plant or mushroom extract orplant or mushroom to provide an equivalent dose. In another aspect, thecomposition comprises 0.01 mg to 0.1 mg, 0.01 mg to 1 mg, 0.1 mg to 10mg, 0.1 mg to 1 mg, 0.5 mg to 1 mg, 0.5 mg to 5 mg, 0.25 mg to 1 mg, 0.2mg to 2 mg, 0.2 mg to 5 mg, or 1 mg to 10 mg of one or more cannabinoidsor an amount of a plant extract or plant or mushroom to provide anequivalent dose. In another aspect, the composition comprises 0.1 mg to1 mg, 1 mg to 10 mg, 10 mg to 100 mg, 10 mg to 50 mg, 50 mg to 100 mg,20 mg to 80 mg, 20 mg to 50 mg, 50 mg to 100 mg, 50 mg to 80 mg, or 10mg to 80 mg of one or more phenethylamines or amphetamines or an amountof a plant or mushroom extract or plant or mushroom to provide anequivalent dose. In another aspect, the composition comprises 0.1 mg to10 mg, 1 mg to 500 mg, 1 mg to 100 mg, 200 mg to 500 mg, 50 mg to 200mg, 10 mg to 50 mg, 50 mg to 200 mg, 1 mg to 200 mg, or 1 mg to 50 mg ofone or more adversives. In another aspect, the composition comprises oneor more pharmaceutically acceptable excipients. In another aspect, thecomposition is a powder admixture, liquid, suspension, or emulsion. Inanother aspect, the composition further comprises one or more extractsor pure chemicals from other fungi comprising one or more of Antrodia,Beauveria, Copelandia, Cordyceps, Fomitopsis, Ganoderma, Grifola,Hericium, Hypsizygus, Inonotus, Isaria, Panaeolus, Phellinus,Piptoporus, Pleurotus, Polyporus or Trametes species or combinationsthereof; a mycelium extract of Antrodia, Beauveria, Copelandia,Cordyceps, Fomitopsis, Ganoderma, Grifola, Hericium, Hypsizygus,Inonotus, Isaria, Panaeolus, Phellinus, Piptoporus, Pleurotus, Polyporusor Trametes species or combinations thereof; or a fruitbody extract ofAntrodia, Beauveria, Copelandia, Cordyceps, Fomitopsis, Ganoderma,Grifola, Hericium, Hypsizygus, Inonotus, Isaria, Panaeolus, Phellinus,Piptoporus, Pleurotus, Polyporus or Trametes species or combinationsthereof. In another aspect, the composition further comprises one ormore extracts or pure chemicals from plant species comprising one ormore of Bacopa species (Bacopa monnien), Gotu kola (Centella asiatica),and Gingko (Gingko biloba, Ginger (Zingiber officinale), Holy Basil(Ocimum sanctum), Hu Zhang (Polygonum cuspidatum), Oregano (Origanumvulgare, Origanum onites), Rosemary (Rosmarinus officinalis, Rosmarinuseriocalyx, species in the genus Rosmarinus), Turmeric (Curcuma longa),Green Tea (Camellia sinensis), lavender (Lavandula spica and relatedspecies in the genus Lavandula), skullcap (Scutellaria lateriflora) oatstraw (Avena sativa, Avena byzantina), Salvia divinorum, aka Diviner'sSage, Banisteriopsis caapi and Psychotria species, plants containingibogaine (Tabemanthe iboga, Voacanga africana and Tabemaemontanaundulate), peyote (Lophophora williamsii), the seeds of morning glory(Ipomoea tricolor and related species) and Hawaiian baby wood rose(Argyreia nervosa), Acacia confusa, Acacia obtusifolia, Acaciasimplicifolia, Desmanthus illinoensis, or Cannabis (Cannabis sativa, C.indica and C. ruderalis), or combinations thereof. In another aspect,the composition is effective to treat, alleviate, prevent or ameliorateserotonin (5-hydroxytryptamine, 5-HT) receptor disorders, psychiatricand mood disorders, e.g., depression, anxiety, major depressivedisorder, treatment resistant depression, persistent depression, manicdepression or bipolar disorder, depressive psychosis, perinataldepression, premenstrual dysphoric disorder, seasonal depressions,situational depression, panic disorder, obsessive compulsive disorder,post-traumatic stress disorder, attention deficit/hyperactivitydisorder, sleep disorders, eating disorders, schizophrenia, personalitydisorders, substance abuse disorders (drug abuse, addiction,alcoholism); neuronal injuries or physical neurodegeneration (e.g.,physical injury, head trauma, spinal cord trauma, concussion, peripheralneuron trauma, paralysis, ischemia, hypoxia, stroke; organophosphates,lead, heavy metals, nerve agents, other toxic compounds, prions, amyloidplaque, neurotoxic viruses, stress); neurodegenerative diseases (e.g.,Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis,multiple sclerosis, frontotemporal dementia, Huntington's disease,adrenal leukodystrophy, Alexander's disease, Alper's disease,Alzheimer's disease, amyotrophic lateral sclerosis, balo concentricsclerosis, Canavan disease, Charcot-Marie-Tooth disease, childhoodataxia with central nervous system hypomyelination, chronic idiopathicperipheral neuropathy, frontotemporal dementia, Huntington's disease,Krabbe disease, monomelic amyotrophy, multiple sclerosis (MS),neurodegeneration, neuromyelitis optica, neuropathic pain,neurosarcoidosis, Parkinson's disease, Pelizaeus-Merzbacher disease,primary lateral sclerosis, progressive supranuclear palsy, radicularpain, radiculopathic pain, Schilder's disease, sciatic pain, sciatica,subacute necrotizing myelopathy, transverse myelitis, or Zellwegersyndrome); congenital or organic cognitive impairment, learningdisabilities, autism spectrum disorder; cognitive enhancement,intelligence enhancement, creativity enhancement, memory improvement,learning enhancement and improvement, spiritual enhancement, “mindexpansion,” IQ improvement, EQ improvement, balance enhancement,athleticism, motor skill enhancement, special navigation, clairvoyance,psychic enhancement, or general improvement of mental health. In anotheraspect, the composition comprises norpsilocin and an extract of extractsor isolates rom Hericium erinaceus. In another aspect, the compositioncomprises baeocystin and an extract of extracts or isolates rom Hericiumerinaceus. In another aspect, the composition comprises norbaeocystinand an extract of extracts or isolates rom Hericium erinaceus.

Another embodiment described herein is a method of treating orpreventing serotonin (5-hydroxytryptamine, 5-HT) receptor disorders,neuronal injuries, neurodegeneration, neurological diseases, congenitalor organic cognitive impairment, learning disabilities, autism spectrumdisorder, psychiatric and mood disorders, cognitive enhancement,physical or motor neuron enhancement, or general improvement of mentalhealth in a subject in need thereof, the method comprising administeringto the subject a therapeutically effective amount of a compositioncomprising one or more tryptamines or in pure form or pharmaceuticallyacceptable salts, hydrates, solvates, prodrugs, stereoisomers, ortautomers thereof, or extracts or isolates from psilocybin containingmushrooms, or combinations thereof combined with one or more erinacinesor hericenones in pure form or pharmaceutically acceptable salts,hydrates, solvates, prodrugs, stereoisomers, or tautomer thereof, orcombinations thereof, extracts or isolates from Hericium mushroomspecies, combinations thereof and one or more pharmaceuticallyacceptable excipients. In one aspect, the composition further comprisesone or more adversive compounds comprising niacin, ipecac, apomorphine,bittering agents (e.g., denatonium benzoate), capsaicin, capsacutindihydrocapsaicin, nordihydrocapsaicin, homocapsaicin,homodihydrocapsaicin, capsaicinoids, gingerol, pipeline, isopiperine,zingerone, shogaol, vanillylamide derivatives, or combinations thereof.

Another embodiment described herein is a method of treating orpreventing serotonin (5-hydroxytryptamine, 5-HT) receptor disorders,neuronal injuries, neurodegeneration, neurological diseases, congenitalor organic cognitive impairment, learning disabilities, autism spectrumdisorder, psychiatric and mood disorders, cognitive enhancement,physical or motor neuron enhancement, or general improvement of mentalhealth in a subject in need thereof, the method comprising administeringto the subject a therapeutically effective amount of a compositioncomprising one or more tryptamines or in pure form or pharmaceuticallyacceptable salts, hydrates, solvates, prodrugs, stereoisomers, tautomersthereof or combinations thereof, or extracts or isolates from psilocybincontaining mushrooms, or combinations thereof combined with one or moreerinacines or hericenones in pure form or pharmaceutically acceptablesalts, hydrates, solvates, prodrugs, stereoisomers, or tautomer thereof,or combinations thereof, extracts or isolates from Hericium mushroomspecies, combinations thereof; one or more cannabinoids in pure form orpharmaceutically acceptable salts, hydrates, solvates, prodrugs,stereoisomers, tautomers thereof, or combinations thereof, or extractsor isolates from Cannabis sativa, Cannabis sativa, Cannabis indica, orCannabis ruderalis; and one or more pharmaceutically acceptableexcipients.

Another embodiment described herein is a method of treating orpreventing serotonin (5-hydroxytryptamine, 5-HT) receptor disorders,neuronal injuries, neurodegeneration, neurological diseases, congenitalor organic cognitive impairment, learning disabilities, autism spectrumdisorder, psychiatric and mood disorders, cognitive enhancement,physical or motor neuron enhancement, or general improvement of mentalhealth in a subject in need thereof, the method comprising administeringto the subject a therapeutically effective amount of a compositioncomprising norpsilocin, norbaeocystin, baeocystin, or psilocybin,combined with one or more erinacines or hericenones in pure form orpharmaceutically acceptable salts, hydrates, solvates, prodrugs,stereoisomers, or tautomer thereof, or combinations thereof, extracts orisolates from Hericium mushroom species, combinations thereof and one ormore pharmaceutically acceptable excipients.

Another embodiment described herein is the use of a pharmaceuticalcomposition comprising one or more tryptamines, erinacines, hericenones,or pharmaceutically acceptable salts, hydrates, solvates, prodrugs,stereoisomers, or tautomers thereof, or combinations thereof and one ormore pharmaceutically acceptable excipients, in the manufacture of amedicament for treatment of serotonin (5-hydroxytryptamine, 5-HT)receptor disorders, neuronal injuries, neurodegeneration, neurologicaldiseases, congenital or organic cognitive impairment, learningdisabilities, autism spectrum disorder, psychiatric and mood disorders,cognitive enhancement, physical or motor neuron enhancement, or generalimprovement of mental health.

Another embodiment described herein is the use of a pharmaceuticalcomposition comprising an effective amount of one or more tryptamines orpharmaceutically acceptable salts, hydrates, solvates, prodrugs,stereoisomers, or tautomers thereof, or combinations thereof and one ormore pharmaceutically acceptable excipients, in the manufacture of amedicament for treating or preventing serotonin (5-hydroxytryptamine,5-HT) receptor disorders, neuronal injuries, neurodegeneration,neurological diseases, congenital or organic cognitive impairment,learning disabilities, autism spectrum disorder, psychiatric and mooddisorders, cognitive enhancement, physical or motor neuron enhancement,or general improvement of mental health.

Another embodiment described herein is the use of a pharmaceuticalcomposition comprising an effective amount of one or more tryptamines,erinacines, hericenones, or pharmaceutically acceptable salts, hydrates,solvates, prodrugs, stereoisomers, or tautomers thereof, or combinationsthereof and one or more pharmaceutically acceptable excipients in themanufacture of a medicament for treating serotonin (5-hydroxytryptamine,5-HT) receptor disorders, neuronal injuries, neurodegeneration,neurological diseases, congenital or organic cognitive impairment,learning disabilities, autism spectrum disorder, psychiatric and mooddisorders, cognitive enhancement, physical or motor neuron enhancement,or general improvement of mental health in a subject in need thereof.

Another embodiment described herein is the use of a pharmaceuticalcomposition comprising an effective amount of one or more tryptamines,erinacines, hericenones, cannabinoids, or pharmaceutically acceptablesalts, hydrates, solvates, prodrugs, stereoisomers, or tautomersthereof, or combinations thereof and one or more pharmaceuticallyacceptable excipients for treating or preventing serotonin(5-hydroxytryptamine, 5-HT) receptor disorders, neuronal injuries,neurodegeneration, neurological diseases, congenital or organiccognitive impairment, learning disabilities, autism spectrum disorder,psychiatric and mood disorders, cognitive enhancement, physical or motorneuron enhancement, or general improvement of mental health in a subjectin need thereof.

Another embodiment described herein is a means for treating orpreventing serotonin (5-hydroxytryptamine, 5-HT) receptor disorders,neuronal injuries, neurodegeneration, neurological diseases, congenitalor organic cognitive impairment, learning disabilities, autism spectrumdisorder, psychiatric and mood disorders, cognitive enhancement,physical or motor neuron enhancement, or general improvement of mentalhealth in a subject in need thereof in in a subject in need thereofcomprising administering a composition comprising an effective amount ofone or more tryptamines, erinacines, hericenones, or pharmaceuticallyacceptable salts, hydrates, solvates, prodrugs, stereoisomers, ortautomers thereof, or combinations thereof and one or morepharmaceutically acceptable excipients to the subject.

Another embodiment described herein is a means for treating orpreventing serotonin (5-hydroxytryptamine, 5-HT) receptor disorders,neuronal injuries, neurodegeneration, neurological diseases, congenitalor organic cognitive impairment, learning disabilities, autism spectrumdisorder, psychiatric and mood disorders, cognitive enhancement,physical or motor neuron enhancement, or general improvement of mentalhealth in a subject in need thereof in in a subject in need thereofcomprising administering a composition comprising an effective amount ofone or more tryptamines, erinacines, hericenones, cannabinoids, orpharmaceutically acceptable salts, hydrates, solvates, prodrugs,stereoisomers, or tautomers thereof, or combinations thereof and one ormore pharmaceutically acceptable excipients to the subject.

Another embodiment described herein is a method for inducing neuronalgrowth and neuronal lengthening comprising administering an effective aneffective amount of one or more tryptamines or in pure form or extractsor isolates from psilocybin containing mushrooms, or combinationsthereof combined with one or more erinacines or hericenones in pureform, extracts or isolates from Hericium mushroom species, orcombinations thereof and one or more pharmaceutically acceptableexcipients to the subject.

Another embodiment described herein is a method for inducing neuronalgrowth and neuronal lengthening comprising administering an effective aneffective amount of one or more or norpsilocin, norbaeocystin,baeocystin, or psilocybin combined with one or more erinacines orhericenones in pure form, extracts or isolates from Hericium mushroomspecies, or combinations thereof and one or more pharmaceuticallyacceptable excipients to the subject.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows the effect of four concentrations of the tryptaminesbaeocystin, norbaeocystin, and norpsilocin on neurite growth relative tothe vehicle control. The norpsilocin 3 and 10 μg/mL experiments are notshown. Data is shown in Table 6.

FIG. 2 shows the effect of selected concentrations of H. erinaceusextract on neurite growth relative to the vehicle control. Data is shownin Table 7.

FIG. 3 shows the effect of norbaeocystin and H. erinaceus extract onneurite growth relative to the vehicle control. Data is shown in Table8.

FIG. 4 shows the effect of norpsilocin and H. erinaceus extract onneurite growth relative to the vehicle control. Data is shown in Table9.

FIG. 5 shows the effect of baeocystin and H. erinaceus extract onneurite growth relative to the vehicle control. Data is shown in Table10.

FIG. 6 shows the plate layout for Neurite Outgrowth 5.

FIG. 7 shows the impact of Hericium erinaceus extracts and psilocybinanalogs on neurite length at day 5.

FIG. 8 shows the impact of Hericium erinaceus extracts and psilocybinanalogs on neurite length at day 7.

FIG. 9 shows the impact of Hericium erinaceus extracts and psilocybinanalogs on neurite length at day 11.

FIG. 10 shows neurite outgrowth induced by HE extracts (Day 7).

FIG. 11 shows a summary of hits from in-house testing of neuriteoutgrowth of PC12 cells treated with conditioned media from 1321N1 cells(n=3).

FIG. 12 shows the ability of FP H. erinaceus extracts to bind to MAPkinases that influence neural health.

FIG. 13 shows the ability of FP H. erinaceus extracts to increaseinterleukin-6 (IL-6) production in peripheral blood mononuclear cells(PBMCs).

FIG. 14 shows that FP H. erinaceus extracts demonstrate radicalscavenging activity in the DPPH assay, indicating they have antioxidantactivity.

FIG. 15 shows SM1-91-C, suspended in MeOH, filtered through apolypropylene 0.22 μM filter (in-house) and suspended in DMEM, filteredthrough a cellulose acetate 0.22 μM Filter (Neurofit preparation;outsourced). Solubilizing and sterilizing the sample in this mannereliminates a lot of the complexity in the ethyl acetate fraction,including the putative erinacine peaks.

FIG. 16 shows induction of NGF protein induced by norbaeocystin in human1321N1 cells (n=3; p<0.05).

FIG. 17 shows Depression Anxiety and Stress Scale (DASS 21)—Range 0-42.F (1,217)=12.44, p<0.001, η2=0.05, F (1,217)=3.99, p<0.05, η2=0.02.

FIG. 18 shows Positive and Negative Affect Scale (PANAS)—Range 10-50. F(1,223)=35.12, p<0.00001, η2=0.13, F (1,223)=13.90, p<0.001, η2=0.06.

FIG. 19 shows that there are no differences in stacking versuspsilocybin alone at 4 weeks—All F (1,141)<1, p>0.5.

DETAILED DESCRIPTION

Described herein are neurotrophic and nootropic compositions and methodsfor treating subjects with such compositions.

As used herein, the term “tryptamine” refers to any compound related toor derived from the monoamine alkaloid 2-(1H-Indol-3-yl)ethanamine(tryptamine), a non-selective 5-HT_(2A) agonist andserotonin-norepinephrine-dopamine releasing agent (SNDRA). Thetryptamine may be a natural product extracted from or isolated from anatural source, such as a Psilocybe mushroom, or synthesizedsynthetically. Exemplary tryptamines include psilocybin, baeocystin,norbaeocystin, psilocin, norpsilocin, 4-hydroxytryptamine,N,N-dimethyltryptamine, 5-hydroxytryptamine (serotonin), tryptamine,N-methyltryptamine, N-methyltryptamine, inter alia, pharmaceuticallyacceptable salts, hydrates, solvates, prodrugs, stereoisomers, ortautomers thereof. Tryptamines such as psilocybin, psilocin, andbaeocystin when in mushrooms from nature are known to decay over time,especially quickly in suboptimal storage conditions. Repke et al., J.Pharmac. Sci. 66(1): 113-114 (1977). In another study, psilocybincontent of P. cubensis ranged from 0.102% to 0.706%, while psilocincontent ranged from 0.415% to 0.836% of dried mushroom tissue. Gambaroet al., J. Pharmac. Biomed. Anal. 125: 427-432 (2016). This variabilityis consistent with trends previously observed, where psilocybin contentof mushroom tissue appeared to increase with subsequent flushes. Bigwoodand Beug, J. Ethnopharmacology 5(3): 287-291 (1982); Beug and Bigwood,J. Ethnopharmacology 5(3): 271-285 (1982). The growing substrate canaffect the tryptamine concentration as well. Gartz found that growingPsilocybe cubensis on a cow dung-rice growing substrate increasedpsilocin content in Psilocybe cubensis from 0.09% to 3.3% of the driedmushroom weight. See Gartz, Planta Med. 55(3): 249-250 (1989). Also,different parts of a mushroom can have different quantities of thesecompounds. For example, one study found that psilocybin is highest inthe caps of Panaeolus subalteatus as compared to the rest of thefruiting body. See Gartz, Biochemie und Physiologie der Pflanzen.184(1-2): 171-178 (1989). In addition to psilocybin and psilocin,several other tryptamine alkaloid compounds can also be present invarying concentrations in mushrooms found in nature. Generally, thesecompounds are part of the same biosynthetic pathway that yieldspsilocybin and can be distinguished from one another based on thepresence or absence of one or more methyl or phosphate groups. Thisunique class of biochemicals is referred to as psilocybin analogs. Fewreports of baeocystin consumption exist. In a 1997 book, Jochen Gartzreported that baeocystin was roughly akin to psilocybin in terms of itspotency and psychotropic effects. The same author had previouslypublished an anecdotal experience where he experienced a “gentlehallucinogenic experience” after consuming 4 mg of baeocystin. SeeGartz, Ann Mus civ Rovereto 7: 265-74 (1991). Additional case studies oforal consumption of 10 mg and 20 mg baeocystin did not produce anyhallucinogenic effects. Even less is understood about norpsilocin,baeocystin's dephosphorylated derivative, which was only recentlyidentified. Lenz et al., J. Nat. Prod. 80(10): 2835-2838 (2017).

As used herein, the terms “phenethylamine” and “amphetamine” refers toany compound related to or derived from the monoamine alkaloids, whichacts as a central nervous system stimulant. The phenethylamines andamphetamines may be natural products extracted from or isolated fromnatural sources or synthetically synthesized. Exemplary phenethylaminesand amphetamines include 3,4,5-trimethoxyphenethylamine (Mescaline),2,5-dimethoxy-4-methylamphetamine (DOM),2,5-dimethoxy-4-bromophenethylamine (2C-B),2,5-dimethoxy-4-ethylphenethylamine (2C-E),2,5-dimethoxy-4-ethylthiophenethylamine (2C-T-2),2,5-dimethoxy-4-propylthiophenethylamine (2C-T-7), p-methoxy-amphetamine(PMA), 2,4-dimethoxy-amphetamine (2,4-DMA), 3,4-dimethoxy-amphetamine(3,4-DMA), 3,4-methylenedioxy-amphetamine (MDA),3-methoxy-4,5-methylendioxy-amphetamine (MMDA),2-methoxy-3,4-methylendioxyamphetamine (MMDA-3a),2-methoxy-4,5-methylendioxyamphetamine (MMDA-2),3,4,5-trimethoxyamphetamine (TMA), 2,4,5-trimethoxyamphetamine (TMA-2),2,5-dimethoxy-3,4-methylenedioxyamphetamine (DMMDA),2,3-dimethoxy-4,5-methylenedioxyamphetamine (DMMDA-2),2,3,4,5-tetramethoxyamphetamine (TeMA),(R)-2,5-dimethoxy-4-iodoamphetamine, inter alia, pharmaceuticallyacceptable salts, hydrates, solvates, prodrugs, stereoisomers, ortautomers thereof.

As used herein, the terms “erinacines” and “hericenones” refer to thecyathin diterpenoids erinacine, hericenone, and related compounds. Thecompounds may be synthetic or natural products isolated from orextracted from H. erinaceus, H. coralloides, H. ramosum. Exemplarycompounds include Erinacine A, Erinacine B, Erinacine C, Erinacine D,Erinacine E, Erinacine F, Erinacine G, Erinacine H, Erinacine I,Erinacine J, Erinacine K, Erinacine P, Erinacine Q, Erinacine R,Erinacol, other Erinacines Hericenone A, Hericenone B, Hericenone C,Hericenone D, Hericenone E, Hericenone F, Hericenone G, Hericenone H,other hericenones, or pharmaceutically acceptable salts, hydrates,solvates, prodrugs, stereoisomers, or tautomers thereof. In contrast topsilocybin mushrooms which primarily grow on the ground in meadows andwoods of the subtropics and tropics, usually in soils rich in humus andplant debris, Hericium erinaceus (Lion's Mane mushrooms) grow on thebark of trees in temperate forests of the Northern United States andCanada, where they are able to withstand cold temperatures and frost.Further, psilocybin mushrooms are terrestrial, whereas Lion's Manemushrooms are non-terrestrial (i.e., they grow on trees). Therefore,Lion's Mane mushrooms and psilocybin mushrooms live in differenthabitats and neither is found cohabitating or combined in nature.

As used herein, the term “cannabinoids” refer to the phytocannabinoidsfrom Cannabis. The compounds may be synthetic or natural productsisolated from or extracted from Cannabis sativa, Cannabis sativa,Cannabis indica, or Cannabis ruderalis. Exemplary compounds includeΔ8-tetrahydrocannabinol, Δ9-tetrahydrocannabinol (THC),tetrahydrocannabinolic acid (THCA), cannabidiol (CBD), cannabidiolicacid (CBDA), cannabinol (CBN), cannabigerol (CBG), cannabichromene(CBC), cannabicyclol (CBL), cannabivarin (CBV), tetrahydrocannabivarin(THCV), cannabidivarin (CBDV), cannabichromevarin (CBCV),cannabigerovarin (CBGV), cannabigerol monomethyl ether (CBGM),cannabielsoin (CBE), cannabicitran (CBT), among others, orpharmaceutically acceptable salts, hydrates, solvates, prodrugs,stereoisomers, or tautomers thereof.

The term “a therapeutically effective amount” of a compound describedherein refers to an amount of the compound described herein that willelicit the biological or medical response of a subject, for example,reduction or inhibition of an enzyme or a protein activity, orameliorate symptoms, alleviate conditions, slow or delay diseaseprogression, or prevent a disease, etc. In one embodiment, the term “atherapeutically effective amount” refers to the amount of the compounddescribed herein that, when administered to a subject, is effective toat least partially alleviate, prevent and/or ameliorate a condition, ora disorder or serotonin (5-hydroxytryptamine, 5-HT) receptor disorders,neuronal injuries, neurodegeneration, neurological diseases, congenitalor organic cognitive impairment, learning disabilities, autism spectrumdisorder, psychiatric and mood disorders, cognitive enhancement,physical or motor neuron enhancement, or general improvement of mentalhealth. In one embodiment, the term “a therapeutically effective amount”refers to the amount of the compound described herein that, whenadministered to a cell, or a tissue, or a non-cellular biologicalmaterial, or a medium, is effective to treat or ameliorate serotonin(5-hydroxytryptamine, 5-HT) receptor disorders, neuronal injuries,neurodegeneration, neurological diseases, congenital or organiccognitive impairment, learning disabilities, autism spectrum disorder,psychiatric and mood disorders, cognitive enhancement, physical or motorneuron enhancement, or general improvement of mental health.

As used herein, the term “subject” refers to an animal. Typically, theanimal is a mammal. A subject also refers to, for example, primates(e.g., humans, male or female; infant, adolescent, or adult), cows,sheep, goats, horses, dogs, cats, rabbits, rats, mice, fish, birds, andthe like. In an embodiment, the subject is a primate. In one embodiment,the subject is a human.

As used herein, the terms “inhibit,” “inhibition,” or “inhibiting” referto the reduction or suppression of a given condition, symptom, ordisorder, or disease, or a significant decrease in the baseline activityof a biological activity or process.

As used herein, the terms “treat”, “treating,” or “treatment” of anydisease or disorder refer In an embodiment, to ameliorating the diseaseor disorder (i.e., slowing or arresting or reducing the development ofthe disease or at least one of the clinical symptoms thereof). In anembodiment, “treat,” “treating,” or “treatment” refers to alleviating orameliorating at least one physical or mental parameter including thosewhich may not be discernible by the subject.

As used herein, the term “preventing” refers to a reduction in thefrequency of, or delay in the onset of, symptoms of the condition ordisease.

As used herein, a subject is “in need of” a treatment if such subjectwould benefit biologically, medically, or in quality of life from suchtreatment.

As used herein, “serotonin (5-hydroxytryptamine, 5-HT) receptordisorders” refers to any disorder or disease that affects serotoninreceptors including neuronal injuries, organic abnormalities,depression, mood disorders, and the like. Serotonin receptors modulatethe release of neurotransmitters such as glutamate, GABA, dopamine,epinephrine, norepinephrine, and acetylcholine, and hormones, includingoxytocin, prolactin, vasopressin, cortisol, corticotropin, substance P,inter alia. Specifically, 5-HT_(2A/C) receptors influence variousbiological and neurological processes such as addiction, anxiety,appetite, locomotion, cognition, imagination, learning, memory, mood,perception, sexual behavior, sleep, thermoregulation, andvasoconstriction. In addition, 5-HT_(2C) is a heteroreceptor fornorepinephrine and dopamine.

As used herein, “mental health” refers to a subject's emotional,psychological, and social well-being. Mental health disorders orproblems refer to disorders affecting cognition, mood, behavior, andhomeostasis. Mental health disorders may be caused by biological factors(genetic or neurochemistry), stress, trauma, or abuse, or associatedwith injury.

The term “alkyl” refers to a radical of a straight chain or branchedsaturated hydrocarbon group having from 1 to 6 carbon atoms (“C₁₋₆alkyl”). In some embodiments, an alkyl group has 1 to 5 carbon atoms(“C₁₋₅ alkyl”). In some embodiments, an alkyl group has 1 to 4 carbonatoms (“C₁₋₄ alkyl”). In some embodiments, an alkyl group has 1 to 3carbon atoms (“C₁₋₃ alkyl”). In some embodiments, an alkyl group has 1to 2 carbon atoms (“C₁₋₂alkyl”). In some embodiments, an alkyl group has1 carbon atom (“C₁ alkyl”). In some embodiments, an alkyl group has 2 to6 carbon atoms (“C₂₋₆ alkyl”). Examples of C₁₋₆ alkyl groups includemethyl (C₁), ethyl (C₂), propyl (C₃) (e.g., n-propyl, isopropyl), butyl(C₄) (e.g., n-butyl, tert-butyl, sec-butyl, isobutyl), pentyl (C₅)(e.g., n-pentyl, 3-pentanyl, amyl, neopentyl, 3-methyl-2-butanyl,tertiary amyl), and hexyl (C₆) (e.g., n-hexyl).

“Alkylene” refers to a divalent radical of an alkyl group, e.g., —CH₂—,—CH₂CH₂—, and —CH₂CH₂CH₂—.

“Heteroalkyl” refers to an alkyl group, which further includes at leastone heteroatom (e.g., 1, 2, 3, or 4 heteroatoms) selected from oxygen,nitrogen, or sulfur within (i.e., inserted between adjacent carbon atomsof) and/or placed at one or more terminal position(s) of the parentchain. In certain embodiments, a heteroalkyl group refers to a saturatedgroup having from 1 to 10 carbon atoms and 1 or more heteroatoms withinthe parent chain (“heteroC₁₋₁₀ alkyl”). In some embodiments, aheteroalkyl group is a saturated group having 1 to 9 carbon atoms and 1or more heteroatoms within the parent chain (“heteroC₁₋₉ alkyl”). Insome embodiments, a heteroalkyl group is a saturated group having 1 to 8carbon atoms and one or more heteroatoms within the parent chain(“heteroC₁₋₈ alkyl”). In some embodiments, a heteroalkyl group is asaturated group having 1 to 7 carbon atoms and one or more heteroatomswithin the parent chain (“heteroC₁0.7 alkyl”). In some embodiments, aheteroalkyl group is a saturated group having 1 to 6 carbon atoms and 1or more heteroatoms within the parent chain (“heteroC₁₋₆ alkyl”). Insome embodiments, a heteroalkyl group is a saturated group having 1 to 5carbon atoms and 1 or 2 heteroatoms within the parent chain (“heteroC₁₋₅alkyl”). In some embodiments, a heteroalkyl group is a saturated grouphaving 1 to 4 carbon atoms and 1 or 2 heteroatoms within the parentchain (“heteroC₁₋₄ alkyl”). In some embodiments, a heteroalkyl group isa saturated group having 1 to 3 carbon atoms and 1 heteroatom within theparent chain (“heteroC₁₋₃ alkyl”). In some embodiments, a heteroalkylgroup is a saturated group having 1 to 2 carbon atoms and 1 heteroatomwithin the parent chain (“heteroC₁₋₂ alkyl”). In some embodiments, aheteroalkyl group is a saturated group having 1 carbon atom and 1heteroatom (“heteroC1 alkyl”). In some embodiments, a heteroalkyl groupis a saturated group having 2 to 6 carbon atoms and 1 or 2 heteroatomswithin the parent chain (“heteroC₂₋₆ alkyl”). Unless otherwisespecified, each instance of a heteroalkyl group is independentlyunsubstituted (an “unsubstituted heteroalkyl”) or substituted (a“substituted heteroalkyl”) with one or more substituents. In certainembodiments, the heteroalkyl group is an unsubstituted heteroC₁₋₁₀alkyl. In certain embodiments, the heteroalkyl group is a substitutedheteroC₁₋₁₀ alkyl.

“Heteroalkylene” refers to a divalent radical of a heteroalkyl group.

“Alkoxy” or “alkoxyl” refers to an —O-alkyl radical. In someembodiments, the alkoxy groups are methoxy, ethoxy, n-propoxy,isopropoxy, n-butoxy, tert-butoxy, sec-butoxy, n-pentoxy, n-hexoxy, and1,2-dimethylbutoxy. In some embodiments, alkoxy groups are lower alkoxy,i.e., with between 1 and 6 carbon atoms. In some embodiments, alkoxygroups have between 1 and 4 carbon atoms.

As used herein, the term “aryl” refers to a stable, aromatic, mono- orbicyclic ring radical having the specified number of ring carbon atoms.Examples of aryl groups include, but are not limited to, phenyl,1-naphthyl, 2-naphthyl, and the like. The related term “aryl ring”likewise refers to a stable, aromatic, mono- or bicyclic ring having thespecified number of ring carbon atoms.

As used herein, the term “heteroaryl” refers to a stable, aromatic,mono- or bicyclic ring radical having the specified number of ring atomsand comprising one or more heteroatoms individually selected fromnitrogen, oxygen, and sulfur. The heteroaryl radical may be bonded via acarbon atom or heteroatom. Examples of heteroaryl groups include, butare not limited to, furyl, pyrrolyl, thienyl, pyrazolyl, imidazolyl,thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl,pyrazinyl, pyridazinyl, pyrimidyl, pyridyl, quinolinyl, isoquinolinyl,indolyl, indazolyl, oxadiazolyl, benzothiazolyl, quinoxalinyl, and thelike. The related term “heteroaryl ring” likewise refers to a stable,aromatic, mono- or bicyclic ring having the specified number of ringatoms and comprising one or more heteroatoms individually selected fromnitrogen, oxygen, and sulfur.

As used herein, the term “carbocycle” refers to a stable, saturated, orunsaturated, non-aromatic, mono- or bicyclic (fused, bridged, or spiro)ring radical having the specified number of ring carbon atoms. Examplesof carbocycle groups include, but are not limited to, the cycloalkylgroups identified above, cyclobutenyl, cyclopentenyl, cyclohexenyl, andthe like. In an embodiment, the specified number is C₃-C₁₂ carbons. Therelated term “carbocyclic ring” likewise refers to a stable, saturated,or unsaturated, non-aromatic, mono- or bicyclic (fused, bridged, orspiro) ring having the specified number of ring carbon atoms.

As used herein, the term “heterocyclyl” refers to a stable, saturated orunsaturated, non-aromatic, mono- or bicyclic (fused, bridged, or spiro)ring radical having the specified number of ring atoms and comprisingone or more heteroatoms individually selected from nitrogen, oxygen andsulfur. The heterocyclyl radical may be bonded via a carbon atom orheteroatom. In an embodiment, the specified number is C₃-C₁₂ carbons.Examples of heterocyclyl groups include, but are not limited to,azetidinyl, oxetanyl, pyrrolinyl, pyrrolidinyl, tetrahydrofuryl,tetrahydrothienyl, piperidyl, piperazinyl, tetrahydropyranyl,morpholinyl, perhydroazepinyl, tetrahydropyridinyl, tetrahydroazepinyl,octahydropyrrolopyrrolyl, and the like. The related term “heterocyclicring” likewise refers to a stable, saturated or unsaturated,non-aromatic, mono- or bicyclic (fused, bridged, or spiro) ring havingthe specified number of ring atoms and comprising one or moreheteroatoms individually selected from nitrogen, oxygen and sulfur.

As used herein, “spirocycloalkyl” or “spirocycle” means carbogenicbicyclic ring systems with both rings connected through a single atom.The rings can be different in size and nature, or identical in size andnature. Examples include spiropentane, spriohexane, spiroheptane,spirooctane, spirononane, or spirodecane. One or both of the rings in aspirocycle can be fused to another ring carbocyclic, heterocyclic,aromatic, or heteroaromatic ring. For example, a (C₃-C₁₂)spirocycloalkylis a spirocycle containing between 3 and 12 carbon atoms.

As used herein, “spiroheterocycloalkyl” or “spiroheterocycle” means aspirocycle wherein at least one of the rings is a heterocycle whereinone or more of the carbon atoms can be substituted with a heteroatom(e.g., one or more of the carbon atoms can be substituted with aheteroatom in at least one of the rings). One or both of the rings in aspiroheterocycle can be fused to another ring carbocyclic, heterocyclic,aromatic, or heteroaromatic ring.

As used herein, “halo” or “halogen” refers to fluorine (fluoro, —F),chlorine (chloro, —Cl), bromine (bromo, —Br), or iodine (iodo, —I).

As used herein, “haloalkyl” means an alkyl group substituted with one ormore halogens. Examples of haloalkyl groups include, but are not limitedto, trifluoromethyl, difluoromethyl, pentafluoroethyl, andtrichloromethyl.

As used herein, “substituted,” whether preceded by the term “optionally”or not, means that one or more hydrogens of the designated moiety arereplaced with a suitable substituent.

As used herein, the definition of each expression, e.g., alkyl, m, n,etc., when it occurs more than once in any structure, is intended to beindependent of its definition elsewhere in the same structure.

The term “prophylaxis” refers to preventing or reducing the progressionof a disorder, either to a statistically significant degree or to adegree detectable to one skilled in the art.

The term “substantially” as used herein means to a great or significantextent, but not completely.

As used herein, all percentages (%) refer to mass (or weight, w/w)percent unless noted otherwise.

The term “about” as used herein refers to any values, including bothintegers and fractional components that are within a variation of up to±10% of the value modified by the term “about.” As used herein, the term“a,” “an,” “the” and similar terms used in the context of the disclosure(especially in the context of the claims) are to be construed to coverboth the singular and plural unless otherwise indicated herein orclearly contradicted by the context. In addition, “a,” “an,” or “the”means “one or more” unless otherwise specified.

Terms such as “include,” “including,” “contain,” “containing,” “having,”and the like mean “comprising.”

The term “or” can be conjunctive or disjunctive.

Definitions of specific functional groups and chemical terms aredescribed in more detail herein. The chemical elements are identified inaccordance with the Periodic Table of the Elements, CAS version,Handbook of Chemistry and Physics, 75^(th) ed., inside cover, andspecific functional groups are generally defined as described therein.Additionally, general principles of organic chemistry, as well asspecific functional moieties and reactivity, are described in ThomasSorrell, Organic Chemistry, University Science Books, Sausalito, 1999;Smith and March, March's Advanced Organic Chemistry, 5^(th) ed, JohnWiley & Sons, Inc., New York, 2001; Larock, Comprehensive OrganicTransformations, VCH Publishers, Inc., New York, 1989; and Carruthers,Some Modern Methods of Organic Synthesis, 3^(rd) ed, CambridgeUniversity Press, Cambridge, 1987.

Certain compounds described herein may exist in particular geometric orstereoisomeric forms. A particular enantiomer of a compound describedherein may be prepared by asymmetric synthesis, or by derivation with achiral auxiliary, where the resulting diastereomeric mixture isseparated and the auxiliary group cleaved to provide the pure desiredenantiomers. Alternatively, where the molecule contains a basicfunctional group, such as amino, or an acidic functional group, such ascarboxyl, diastereomeric salts are formed with an appropriateoptically-active acid or base, followed by resolution of thediastereomers thus formed by fractional crystallization orchromatographic means well known in the art, and subsequent recovery ofthe pure enantiomers.

Unless otherwise stated, structures depicted herein are also meant toinclude geometric (or conformational) forms of the structure; forexample, the R and S configurations for each asymmetric center, Z and Edouble bond isomers, and Z and E conformational isomers. Therefore,single stereochemical isomers as well as enantiomeric, diastereomeric,and geometric (or conformational) mixtures of the disclosed compoundsare within the scope of the disclosure. Unless otherwise stated, alltautomeric forms of the compounds described herein are within the scopeof the disclosure. Additionally, unless otherwise stated, structuresdepicted herein are also meant to include compounds that differ only inthe presence of one or more isotopically enriched atoms. For example,compounds having the disclosed structures including the replacement ofhydrogen by deuterium or tritium, or the replacement of a carbon by a¹³C- or ¹⁴C-enriched carbon are within the scope of this disclosure.Such compounds are useful, for example, as analytical tools, as probesin biological assays, or as therapeutic agents in accordance with thedisclosure.

The “enantiomeric excess” or “% enantiomeric excess” of a compositioncan be calculated using the equation shown below. In the example shownbelow a composition contains 90% of one enantiomer, e.g., the Senantiomer, and 10% of the other enantiomer, i.e., the R enantiomer.ee=(90−10)/100×100=80%.

Thus, a composition containing 90% of one enantiomer and 10% of theother enantiomer is said to have an enantiomeric excess of 80%. Thecompounds or compositions described herein may contain an enantiomericexcess of at least 50%, 75%, 90%, 95%, or 99% of one form of thecompound, e.g., the S-enantiomer. In other words, such compounds orcompositions contain an enantiomeric excess of the S enantiomer over theR enantiomer.

Where a particular enantiomer is preferred, it may, in some embodimentsbe provided substantially free of the corresponding enantiomer and mayalso be referred to as “optically enriched.” “Optically enriched,” asused herein, means that the compound is made up of a significantlygreater proportion of one enantiomer. In certain embodiments, thecompound is made up of at least about 90% by weight of a preferredenantiomer. In other embodiments, the compound is made up of at leastabout 95%, 98%, or 99% by weight of a preferred enantiomer. Preferredenantiomers may be isolated from racemic mixtures by any method known tothose skilled in the art, including chiral high-pressure liquidchromatography (HPLC) and the formation and crystallization of chiralsalts or prepared by asymmetric syntheses. See e.g., Jacques et al.,Enantiomers, Racemates and Resolutions (Wiley Interscience, New York,1981); Wien, et al., Tetrahedron 33:2725 (1977); Eliel, E. L.Stereochemistry of Carbon Compounds (McGraw Hill, N Y, 1962); Wien, S.H. Tables of Resolving Agents and Optical Resolutions p. 268 (E. L.Eliel, Ed., Univ. of Notre Dame Press, Notre Dame, Ind. 1972).

All methods described herein can be performed in any suitable orderunless otherwise indicated herein or otherwise clearly contradicted bycontext. The use of any and all examples, or exemplary language (e.g.,“such as”) provided herein is intended merely to better illuminate thedisclosure and does not pose a limitation on the scope of the disclosureotherwise claimed.

Any resulting mixtures of isomers can be separated based on thephysicochemical differences of the constituents, into the pure orsubstantially pure geometric or optical isomers, diastereomers,racemates, for example, by chromatography and/or fractionalcrystallization.

Any resulting racemates of final products or intermediates can beresolved into the optical antipodes by known methods, e.g., byseparation of the diastereomeric salts thereof, obtained with anoptically active acid or base, and liberating the optically activeacidic or basic compound.

In particular, a basic moiety may thus be employed to resolve thecompounds described herein into their optical antipodes, e.g., byfractional crystallization of a salt formed with an optically activeacid, e.g., tartaric acid, dibenzoyl tartaric acid, diacetyl tartaricacid, di-0,0′-p-toluoyl tartaric acid, mandelic acid, malic acid orcamphor-10-sulfonic acid. Racemic products can also be resolved bychiral chromatography, e.g., high pressure liquid chromatography (HPLC)using a chiral adsorbent.

Various exemplary embodiments of the disclosure are described herein. Itwill be recognized that features specified in each embodiment may becombined, substituted, or replaced with other specified featuresdisclosed elsewhere in the specification to provide further embodimentsof the present disclosure. All analagous compounds may be substitutedfor each other in the same or similar amounts (mass, concentration, ordosages) as indicated for analagous compounds.

It is understood that in the following embodiments, combinations ofsubstituents or variables of the depicted formulae are permissible onlyif such combinations result in stable compounds.

Pharmaceutically Acceptable Salts

Pharmaceutically acceptable salts of the compounds described herein arealso contemplated for the uses described herein. As used herein, theterms “salt” or “salts” refer to an acid addition or base addition saltof a compound described herein. “Salts” include in particular“pharmaceutical acceptable salts.” The term “pharmaceutically acceptablesalts” refers to salts that retain the biological effectiveness andproperties of the compounds disclosed herein and, which typically arenot biologically or otherwise undesirable. In many cases, the compoundsdisclosed herein can form acid and/or base salts by virtue of thepresence of amino and/or carboxyl groups or groups similar thereto.

Pharmaceutically acceptable acid addition salts can be formed withinorganic acids and organic acids.

Inorganic acids from which salts can be derived include, for example,hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid,phosphoric acid, and the like.

Organic acids from which salts can be derived include, for example,acetic acid, propionic acid, glycolic acid, oxalic acid, maleic acid,malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid,benzoic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid,toluenesulfonic acid, sulfosalicylic acid, and the like.

Pharmaceutically acceptable base addition salts can be formed withinorganic and organic bases. Inorganic bases from which salts can bederived include, for example, ammonium salts and metals from columns Ito XII of the periodic table. In certain embodiments, the salts arederived from sodium, potassium, ammonium, calcium, magnesium, iron,silver, zinc, and copper; particularly suitable salts include ammonium,potassium, sodium, calcium, and magnesium salts. Organic bases fromwhich salts can be derived include, for example, primary, secondary, andtertiary amines, substituted amines including naturally occurringsubstituted amines, cyclic amines, basic ion exchange resins, and thelike. Certain organic amines include isopropylamine, benzathine,cholinate, diethanolamine, diethylamine, lysine, meglumine, piperazine,and tromethamine.

Another embodiment is a tryptamine, phenethylamine, amphetamine,erinacine, hericenone, or cannabinoid as an acetate, ascorbate, adipate,aspartate, benzoate, besylate, bromide/hydrobromide,bicarbonate/carbonate, bisulfate/sulfate, camphorsulfonate, caprate,chloride/hydrochloride, chlortheophyllonate, citrate, ethandisulfonate,fumarate, gluceptate, gluconate, glucuronate, glutamate, glutarate,glycolate, hippurate, hydroiodide/iodide, isethionate, lactate,lactobionate, laurylsulfate, malate, maleate, malonate, mandelate,mesylate, methylsulphate, mucate, naphthoate, napsylate, nicotinate,nitrate, octadecanoate, oleate, oxalate, palmitate, pamoate,phosphate/hydrogen phosphate/dihydrogen phosphate, polygalacturonate,propionate, sebacate, stearate, succinate, sulfosalicylate, sulfate,tartrate, tosylate, trifenatate, trifluoroacetate, or xinafoate saltform.

Pharmaceutical Compositions

Another embodiment is a pharmaceutical composition comprising one ormore compounds described herein or a pharmaceutically acceptable salt,hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, and one ormore pharmaceutically acceptable carrier(s). The term “pharmaceuticallyacceptable carrier” refers to a pharmaceutically acceptable material,composition, or vehicle, such as a liquid or solid filler, diluent,excipient, solvent, or encapsulating material, involved in carrying ortransporting any subject composition or component thereof. Each carriermust be “acceptable” in the sense of being compatible with the subjectcomposition and its components and not injurious to the patient Someexamples of materials which may serve as pharmaceutically acceptablecarriers include: (1) sugars, such as lactose, glucose and sucrose; (2)starches, such as corn starch and potato starch; (3) cellulose, and itsderivatives, such as sodium carboxymethyl cellulose, ethyl cellulose andcellulose acetate; (4) powdered tragacanth; (5) malt; (6) gelatin; (7)talc; (8) excipients, such as cocoa butter and suppository waxes; (9)oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil,olive oil, corn oil and soybean oil; (10) glycols, such as propyleneglycol; (11) polyols, such as glycerin, sorbitol, mannitol andpolyethylene glycol; (12) esters, such as ethyl oleate and ethyllaurate; (13) agar; (14) buffering agents, such as magnesium hydroxideand aluminum hydroxide; (15) alginic acid; (16) pyrogen-free water; (17)isotonic saline; (18) Ringer's solution; (19) ethyl alcohol; (20)phosphate buffer solutions; and (21) other non-toxic compatiblesubstances employed in pharmaceutical formulations.

The compositions described herein may be administered orally,parenterally, by inhalation spray, topically, rectally, nasally,buccally, vaginally or via an implanted reservoir. The term “parenteral”as used herein includes subcutaneous, intravenous, intramuscular,intra-articular, intra-synovial, intrasternal, intrathecal,intrahepatic, intralesional and intracranial injection or infusiontechniques. In some embodiments, the compositions of the disclosure areadministered orally, intraperitoneally, or intravenously. Sterileinjectable forms of the compositions of this disclosure may be aqueousor oleaginous suspension. These suspensions may be formulated accordingto techniques known in the art using suitable dispersing or wettingagents and suspending agents. The sterile injectable preparation mayalso be a sterile injectable solution or suspension in a non-toxicparenterally acceptable diluent or solvent, for example as a solution in1,3-butanediol. Among the acceptable vehicles and solvents that may beemployed are water, Ringer's solution, and isotonic sodium chloridesolution. In addition, sterile, fixed oils are conventionally employedas a solvent or suspending medium.

For this purpose, any bland fixed oil may be employed includingsynthetic mono- or di-glycerides. Fatty acids, such as oleic acid andits glyceride derivatives are useful in the preparation of injectables,as are natural pharmaceutically acceptable oils, such as olive oil orcastor oil, especially in their polyoxyethylated versions. These oilsolutions or suspensions may also contain a long-chain alcohol diluentor dispersant, such as carboxymethyl cellulose or similar dispersingagents that are commonly used in the formulation of pharmaceuticallyacceptable dosage forms including emulsions and suspensions. Othercommonly used surfactants, such as Tween®, Spans and other emulsifyingagents or bioavailability enhancers which are commonly used in themanufacture of pharmaceutically acceptable solid, liquid, or otherdosage forms may also be used for the purposes of formulation.

The pharmaceutically acceptable compositions described herein may beorally administered in any orally acceptable dosage form including, butnot limited to, capsules, tablets, aqueous suspensions, or solutions. Inthe case of tablets for oral use, carriers commonly used include lactoseand corn starch. Lubricating agents, such as magnesium stearate, arealso typically added. For oral administration in a capsule form, usefuldiluents include lactose and dried cornstarch. When aqueous suspensionsare required for oral use, the active ingredient is combined withemulsifying and suspending agents. If desired, certain sweetening,flavoring, or coloring agents may also be added.

Alternatively, the pharmaceutically acceptable compositions of thisdisclosure may be administered in the form of suppositories for rectaladministration. These can be prepared by mixing the agent with asuitable non-irritating excipient that is solid at room temperature butliquid at rectal temperature and therefore will melt in the rectum torelease the drug. Such materials include cocoa butter, beeswax, andpolyethylene glycols.

The pharmaceutically acceptable compositions of this disclosure may alsobe administered topically, especially when the target of treatmentincludes areas or organs readily accessible by topical application,including diseases of the eye, the skin, or the lower intestinal tract.Suitable topical formulations are readily prepared for each of theseareas or organs. Topical application for the lower intestinal tract canbe administered using a rectal suppository formulation (see above) or asuitable enema formulation. Topically transdermal patches may also beused.

For topical applications, the pharmaceutically acceptable compositionsmay be formulated in a suitable ointment containing the active componentsuspended or dissolved in one or more carriers. Carriers for topicaladministration of the compounds of this disclosure include, but are notlimited to, mineral oil, liquid petrolatum, white petrolatum, propyleneglycol, polyoxyethylene, polyoxypropylene compound, emulsifying wax, andwater. Alternatively, the pharmaceutically acceptable compositions canbe formulated in a suitable lotion or cream containing the activecomponents suspended or dissolved in one or more pharmaceuticallyacceptable carriers. Suitable carriers include, but are not limited to,mineral oil, sorbitan monostearate, polysorbate 60, cetyl esters wax,cetearyl alcohol, 2-octyldodecanol, benzyl alcohol, and water.

The pharmaceutically acceptable compositions of this disclosure may alsobe administered by nasal aerosol or inhalation. Such compositions areprepared according to techniques known in the art of pharmaceuticalformulation and may be prepared as solutions in saline, employing benzylalcohol or other suitable preservatives, absorption promoters to enhancebioavailability, fluorocarbons, or other conventional solubilizing ordispersing agents. The amount of the compounds of the present disclosurethat may be combined with the carrier materials to produce a compositionin a single dosage form will vary depending upon the host treated andthe mode of administration. Preferably, the compositions should beformulated so that a dosage of between 0.01-100 mg/kg body weight/day ofthe inhibitor can be administered to a patient receiving thesecompositions.

Isotopically Labelled Compounds

A compound described herein or a pharmaceutically acceptable salt,hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, is alsointended to represent unlabeled forms as well as isotopically labeledforms of the compounds. Isotopically labeled compounds have structuresdepicted by the formulas given herein except that one or more atoms arereplaced by an atom having a selected atomic mass or mass number.Examples of isotopes that can be incorporated into compounds describedherein include isotopes of hydrogen, carbon, nitrogen, oxygen,phosphorous, fluorine, and chlorine, such as ²H, ³H, ¹¹C, ¹³C, ¹⁴C, ¹⁵N,¹⁸F, ³¹P ³²P, ³⁵S, ³⁶Cl, ¹²³I, ¹²⁴I, ¹²⁵I, respectively. The disclosureincludes various isotopically labeled compounds as defined herein, forexample, those into which radioactive isotopes, such as ³H and ¹⁴C, orthose into which non-radioactive isotopes, such as ²H and ¹³C arepresent. Such isotopically labelled compounds are useful in metabolicstudies (with ¹⁴C), reaction kinetic studies (with, for example ²H or³H), detection or imaging techniques, such as positron emissiontomography (PET) or single-photon emission computed tomography (SPECT)including drug or substrate tissue distribution assays, or inradioactive treatment of patients. An ¹⁸F or labeled compound may beparticularly desirable for PET or SPECT studies. Isotopically-labeledcompounds described herein or a pharmaceutically acceptable salt,hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, cangenerally be prepared by conventional techniques known to those skilledin the art or by processes analogous to those described herein using anappropriate isotopically-labeled reagents in place of the non-labeledreagent previously employed.

Further, substitution with heavier isotopes, particularly deuterium(i.e., ²H or D) may afford certain therapeutic advantages resulting fromgreater metabolic stability, for example, increased in vivo half-life orreduced dosage requirements or an improvement in therapeutic index. Itis understood that deuterium in this context is regarded as asubstituent of a compound described herein or a pharmaceuticallyacceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomerthereof. The concentration of such a heavier isotope, specificallydeuterium, may be defined by the isotopic enrichment factor. The term“isotopic enrichment factor” as used herein means the ratio between theisotopic abundance and the natural abundance of a specified isotope.

Dosages

Toxicity and therapeutic efficacy of compounds described herein,including pharmaceutically acceptable salts and deuterated variants, canbe determined by standard pharmaceutical procedures in cell cultures orexperimental animals. The LD₅₀ is the dose lethal to 50% of thepopulation. The ED₅₀ is the dose therapeutically effective in 50% of thepopulation. The dose ratio between toxic and therapeutic effects(LD₅₀/ED₅₀) is the therapeutic index. Compounds that exhibit largetherapeutic indexes are preferred. While compounds that exhibit toxicside effects may be used, care should be taken to design a deliverysystem that targets such compounds to the site of affected tissue inorder to minimize potential damage to uninfected cells and therebyreduce side effects.

Data obtained from the cell culture assays and animal studies can beused in formulating a range of dosage for use in humans. The dosage ofsuch compounds may lie within a range of circulating concentrations thatinclude the ED₅₀ with little or no toxicity. The dosage may vary withinthis range depending upon the dosage form employed and the route ofadministration utilized. For any compound, the therapeutically effectivedose can be estimated initially from cell culture assays. A dose may beformulated in animal models to achieve a circulating plasmaconcentration range that includes the IC₅₀ (i.e., the concentration ofthe test compound that achieves a half-maximal inhibition of symptoms)as determined in cell culture. Such information can be used to moreaccurately determine useful doses in humans. Levels in plasma may bemeasured, for example, by high performance liquid chromatography.

It should also be understood that a specific dosage and treatmentregimen for any particular patient will depend upon a variety offactors, including the activity of the specific compound employed, theage, body weight, general health, sex, diet, time of administration,rate of excretion, drug combination, and the judgment of the treatingphysician and the severity of the particular disease being treated. Theamount of a compound described herein in the composition will alsodepend upon the particular compound in the composition.

Methods of Use

Another embodiment is a method of treating or preventing neuronalinjuries, neurodegeneration, neurological diseases, congenital ororganic cognitive impairment, learning disabilities, autism spectrumdisorder, psychiatric and mood disorders, cognitive enhancement,physical or motor neuron enhancement, or general improvement of mentalhealth in a subject in need thereof, the method comprising administeringto the subject a therapeutically effective amount of a compounddisclosed herein, or a pharmaceutically acceptable salt, hydrate,solvate, prodrug, stereoisomer, or tautomer thereof.

Another embodiment is a composition comprising a tryptamine, anerinacine, a hericenone, a cannabinoid, or a pharmaceutically acceptablesalt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, or acombination thereof, and a pharmaceutically acceptable carrier, for usein treating neuronal injuries, neurodegeneration, neurological diseases,congenital or organic cognitive impairment, learning disabilities,autism spectrum disorder, psychiatric and mood disorders, cognitiveenhancement, physical or motor neuron enhancement, or generalimprovement of mental health in a subject in need thereof.

Another embodiment is a composition comprising a tryptamine, anerinacine, a hericenone, a cannabinoid, or a pharmaceutically acceptablesalt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, or acombination thereof, and a pharmaceutically acceptable carrier, for usein treating neuronal injuries, neurodegeneration, neurological diseases,congenital or organic cognitive impairment, learning disabilities,autism spectrum disorder, psychiatric and mood disorders, cognitiveenhancement, physical or motor neuron enhancement, or generalimprovement of mental health in a subject in need thereof.

Another embodiment is a pharmaceutical composition comprising atryptamine, an erinacine, a hericenone, a cannabinoid, or apharmaceutically acceptable salt, hydrate, solvate, prodrug,stereoisomer, or tautomer thereof, or a combination thereof, and apharmaceutically acceptable carrier, for use in treating neuronalinjuries, neurodegeneration, neurological diseases, congenital ororganic cognitive impairment, learning disabilities, autism spectrumdisorder, psychiatric and mood disorders, cognitive enhancement,physical or motor neuron enhancement, or general improvement of mentalhealth in a subject in need thereof.

Another embodiment is a composition comprising a tryptamine, anerinacine, a hericenone, a cannabinoid, or a pharmaceutically acceptablesalt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, or acombination thereof, for use in treating neuronal injuries,neurodegeneration, neurological diseases, congenital or organiccognitive impairment, learning disabilities, autism spectrum disorder,psychiatric and mood disorders, cognitive enhancement, physical or motorneuron enhancement, or general improvement of mental health in a subjectin need thereof. In another embodiment, the composition is useful fortreating or preventing a neurological disorder, a respiratory disorder,a proliferative disorder, an autoimmune disorder, an autoinflammatorydisorder, an inflammatory disorder, or an infectious disease ordisorder.

Another embodiment is the use of a composition comprising a tryptamine,an erinacine, a hericenone, a cannabinoid, or a pharmaceuticallyacceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomerthereof, or a combination thereof, in the manufacture of a medicamentfor treatment of neuronal injuries, neurodegeneration, neurologicaldiseases, congenital or organic cognitive impairment, learningdisabilities, autism spectrum disorder, psychiatric and mood disorders,cognitive enhancement, physical or motor neuron enhancement, or generalimprovement of mental health.

Another embodiment is the use of a pharmaceutical composition comprisinga tryptamine, an erinacine, a hericenone, a cannabinoid, or apharmaceutically acceptable salt, hydrate, solvate, prodrug,stereoisomer, or tautomer thereof, or a combination thereof and apharmaceutically acceptable carrier, in the manufacture of a medicamentfor treating neuronal injuries, neurodegeneration, neurologicaldiseases, congenital or organic cognitive impairment, learningdisabilities, autism spectrum disorder, psychiatric and mood disorders,cognitive enhancement, physical or motor neuron enhancement, or generalimprovement of mental health in a subject in need thereof.

Another embodiment is a use of a pharmaceutical composition comprising atryptamine, an erinacine, a hericenone, a cannabinoid, or apharmaceutically acceptable salt, hydrate, solvate, prodrug,stereoisomer, or tautomer thereof, a combination thereof in themanufacture of a medicament for treating or preventing neuronalinjuries, neurodegeneration, neurological diseases, congenital ororganic cognitive impairment, learning disabilities, autism spectrumdisorder, psychiatric and mood disorders, cognitive enhancement,physical or motor neuron enhancement, or general improvement of mentalhealth in a subject in need thereof.

Another embodiment is a method for treating or preventing neuronalinjuries, neurodegeneration, neurological diseases, congenital ororganic cognitive impairment, learning disabilities, autism spectrumdisorder, psychiatric and mood disorders, cognitive enhancement,physical or motor neuron enhancement, or general improvement of mentalhealth in a subject in need thereof in in a subject in need thereofcomprising administering a composition comprising a tryptamine, anerinacine, a hericenone, a cannabinoid, or a pharmaceutically acceptablesalt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, or acombination thereof to the subject.

Another embodiment is a use of a compound comprising a tryptamine, anerinacine, a hericenone, a cannabinoid, or a pharmaceutically acceptablesalt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, inthe manufacture of a medicament for treating or preventing neuronalinjuries, neurodegeneration, neurological diseases, congenital ororganic cognitive impairment, learning disabilities, autism spectrumdisorder, psychiatric and mood disorders, cognitive enhancement,physical or motor neuron enhancement, or general improvement of mentalhealth.

Another embodiment is the addition of a monamine oxidase inhibitor, suchas P-carbolines (e.g., harmane, harmine, nor harmine, perlolyrine,harmol, cordysinin, inter alia), to any of the above mentionedcompositions or methods to enhance the pharmaceutical efficacy of thetryptamine(s).

Combination Therapies

Another embodiment is a pharmaceutical combination comprising one ormore of a tryptamine, an erinacine, a hericenone, a cannabinoid, or apharmaceutically acceptable salt, hydrate, solvate, prodrug,stereoisomer, or tautomer thereof, a combination thereof, and one ormore additional therapeutic agent(s) for simultaneous, separate orsequential use in therapy for neuronal injuries, neurodegeneration,neurological diseases, congenital or organic cognitive impairment,learning disabilities, autism spectrum disorder, psychiatric and mooddisorders, cognitive enhancement, physical or motor neuron enhancement,or general improvement of mental health. In one embodiment, theadditional therapeutic agent is selected from the group consisting of:an antiproliferative agent, anticancer agent, immunomodulatory agent, ananti-inflammatory agent, a neurological treatment agent, an anti-viralagent, an anti-fungal agent, anti-parasitic agent, an antibiotic, and ageneral anti-infective agent.

One embodiment described herein is neurotrophic and nootropiccompositions and methods for treating subjects with such compositions.In one aspect the composition comprises one or more tryptamines or inpure form or extracts from psilocybin containing mushrooms, orcombinations thereof combined with one or more phenethylamines oramphetamines in pure form or extract from a plant or mushroom, orcombinations thereof, one or more erinacines or hericenones in pureform, extracts from Hericium mushroom species (e.g., H. erinaceus, H.coralloides, H. ramosum) or combinations thereof, one or morecannabinoids in pure form or extracts from Cannabis sativa, Cannabissativa, Cannabis indica, or Cannabis ruderalis, optionally, one or moreadversive compounds such as niacin, capsaicin, ipecac, apomorphine,bittering agents (e.g., denatonium benzoate), inter alia, and one ormore pharmaceutically acceptable excipients.

In one embodiment, the composition is described in Table 1. Compositionsmay contain one or more species or combinations of any of the specieslisted in Table 1.

TABLE 1 Exemplary neurotropic or nootropic compositions ComponentExample Dosage Tryptamine neurotrophics, Psilocybin, baeocystin,norbaeocystin, 10 ng to 10 mg tryptamine derivatives, psilocin,norpsilocin, 4-hydroxytryptamine, esters, or salts thereof, orN,N-dimethyltryptamine, N-methyltryptamine, extracts from fungi or interalia; In addition or alternatively, 3,4,5- plants; In addition to ortrimethoxyphenethylamine (Mescaline), 2,4- alternatively,dimethoxy-amphetamine (2,4-DMA), 3,4- phenethylamines,dimethoxy-amphetamine (3,4-DMA), 3,4- amphetamines;methylenedioxy-amphetamine (MDA), 3- derivatives thereof,methoxy-4,5-methylendioxy-amphetamine extracts from fungi or (MMDA),inter alia plants Optional secondary Erinacines, hericenones,cannabidiol, 10 ng to 500 mg neurotrophic fungal or cannabichromene,cannabigerol, Δ8- plant extracts, or purified tetrahydrocannabinol, Δ9-compounds thereof tetrahydrocannabinol, cannabinol, Optional neurotropicor tetrahydrocannabivarin, cannabidiol-2′,6′- 10 μg to 500 mg nootropicfungal or plant dimethyl ether, Ketamine, inter alia extracts, or othernatural Antrodia, Beauveria, Copelandia, Cordyceps. products, orpurified Fomitopsis, Ganoderma, Grifola, Hericium, compounds thereofHypsizygus, Inonotus, Isaria, Panaeolus, Phellinus, Phellinus,Piptoporus, Pleurotus, Polyporus, Pochonia chiamydosporia, or Trametesspecies or combinations thereof; Bacopa monnien, Centella asiatica,Gingko biloba, Zingiber officinale, Ocimum sanctum, Polygonumcuspidatum, Origanum vulgare, Origanum onites, Rosmarinus officinalis,Rosmarinus eriocalyx, Curcuma longa, Camellia sinensis, Psychotriaviridis, inter alia Optional MAO inhibitor β-carbolines (e.g., harmane,harmine, nor 10 ng to 10 mg compounds harmine, perlolyrine, harmol,cordysinin, inter alia) Optional adversive Niacin, capsaicin, ipecac,apomorphine, 10 μg to 200 mg bittering agents (e.g., denatoniumbenzoate) inter alia Optional pharmaceutical Fillers, binders, diluents,vehicles, lubricants, quantum sufficit excipients preservatives,flavors, colors, etc. Compositions may contain one or more species orcombinations of any of the species listed above. Compositions can beliquid, suspensions, emulsions, dry powder admixtures, or combinationsthereof.

One embodiment described herein is a composition comprising one or moretryptamines such as psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine),baeocystin, (4-phosphoryloxy-N-methyltryptamine), norbaeocystin(4-phosphoryloxy-tryptamine), psilocin(4-hydroxy-N,N-dimethyltryptamine, norpsilocin(4-hydroxy-N-methyl-tryptamine), N,N-dimethyltryptamine,4-hydroxytryptamine, inter alia, in pure form or comprising extractsfrom Psilocybe and psilocybin containing mushrooms, or combinationsthereof.

Another embodiment is a composition of one or more tryptamines or inpure form or extracts from psilocybin containing mushrooms, orcombinations thereof, and further combined with one or more adversivecompounds such as niacin, ipecac, apomorphine, bittering agents (e.g.,denatonium benzoate), capsaicin, capsacutin dihydrocapsaicin,nordihydrocapsaicin, homocapsaicin, homodihydrocapsaicin, capsaicinoids,gingerol, pipeline, isopiperine, zingerone, shogaol, vanillylamidederivatives, or combinations thereof, inter alia.

Another embodiment is a composition of one or more tryptamines or inpure form or extracts from psilocybin containing mushrooms, orcombinations thereof combined with one or more erinacines or hericenonesin pure form, extracts from Hericium mushroom species, or combinationsthereof.

Another embodiment is a composition of one or more tryptamines or inpure form or extracts from psilocybin containing mushrooms, orcombinations thereof combined with one or more erinacines or hericenonesin pure form, extracts from Hericium mushroom species (e.g., H.erinaceus, H. coralloides, H. ramosum) or combinations thereof, andfurther combined with one or more adversive compounds such as niacin,capsaicin, ipecac, apomorphine, bittering agents (e.g., denatoniumbenzoate), inter alia.

Another embodiment is a composition of one or more tryptamines or inpure form or extracts from psilocybin containing mushrooms, orcombinations thereof combined with one or more phenethylamines oramphetamines in pure form or extract from a plant or mushroom, orcombinations thereof, one or more erinacines or hericenones in pureform, extracts from Hericium mushroom species (e.g., H. erinaceus, H.coralloides, H. ramosum) or combinations thereof, and further combinedwith one or more adversive compounds such as niacin, capsaicin, ipecac,apomorphine, bittering agents (e.g., denatonium benzoate), inter alia.

Another embodiment is a composition of one or more tryptamines or inpure form or extracts from psilocybin containing mushrooms, orcombinations thereof combined with one or more cannabinoids in pure formor extracts from Cannabis sativa, Cannabis sativa, Cannabis indica, orCannabis ruderalis.

Another embodiment is a composition of one or more tryptamines or inpure form or extracts from psilocybin containing mushrooms, orcombinations thereof combined with one or more cannabinoids in pure formor extracts from Cannabis sativa, Cannabis sativa, Cannabis indica, orCannabis ruderalis, and further combined with one or more adversivecompounds such as niacin, capsaicin, ipecac, apomorphine, bitteringagents (e.g., denatonium benzoate), inter alia.

Another embodiment is a composition of one or more tryptamines or inpure form or extracts from psilocybin mushrooms containing fungi,extracts thereof or pure chemicals thereof; or plant extracts, or purechemicals thereof, or combinations thereof.

One embodiment is a composition of one or more tryptamines or in pureform or extracts from psilocybin mushrooms combined with one or moreextracts or pure chemicals from other fungi comprising one or more ofAntrodia, Beauveria, Copelandia, Cordyceps, Fomitopsis, Ganoderma,Grifola, Hericium, Hypsizygus, Inonotus, Isaria, Panaeolus, PhellinusPiptoporus, Pleurotus, Polyporus or Trametes species or combinationsthereof; a mycelium extract of Antrodia, Beauveria, Copelandia,Cordyceps, Ganoderma, Fomitopsis, Grifola, Hericium, Hypsizygus,Inonotus, Isaria, Panaeolus, Phellinus, Piptoporus, Pleurotus, Polyporusor Trametes species, or combinations thereof; or a fruitbody extract ofAntrodia, Beauveria, Copelandia, Cordyceps, Fomitopsis, Ganoderma,Grifola, Hericium, Hypsizygus, Inonotus, Isaria, Panaeolus, Phellinus,Piptoporus, Pleurotus, Polyporus or Trametes species, or combinationsthereof.

In one aspect described herein, the fungi comprise one of more ofAntrodia camphoratus, Antrodia cinnamomea, Fomitopsis officinalis,Ganoderma annulare, Ganoderma applanatum, Ganoderma brownii, Ganodermalucidum, Ganoderma lingzhi, Ganoderma resinaceum, Hypsizygus tessulatus,Hypsizygus ulmarius, Inonotus obliquus, Trametes versicolor, Pochoniachlamydosporia, or Pleurotus ostreatus.

In another aspect described herein, the fungi comprise one or more ofAgaricus augustus, Agaricus blazei, Agaricus bonardii, Agaricusbrasiliensis, Agaricus campestris, Agaricus lilaceps, Agaricussubrufescens, Agaricus sylvicola, Agrocybe aegerita, Agrocybe arvalis,Agrocybe pediades, Agrocybe praecox, Antrodia cinnamonea, Clitocybeodora, Conocybe cyanopus, Conocybe lacteus, Conocybe rickenii, Conocybesmithii, Conocybe tenera, Coprinopsis lagopus, Coprinopsis nivea,Coprinus comatus, Coprinus micaceus, Fomitiporia robusta, Fomitopsisofficinalis (Laricifomes officinalis), Ganoderma atrum, Ganodermabrownii, Ganoderma curtisii, Ganoderma lingzhi, Ganoderma oregonense,Ganoderma tsugae, Gymnopus hydrophilus, Gymnopus peronatus, Hericiumerinaceus, Hericium coralloides, Hericium ramosum, Heterobasidionannosum, Hypholoma aurantiaca (Leratiomyces ceres), Hypholoma capnoides,Hypholoma sublateritium, Hypsizygus marmoreus, Hypsizygus tessulatus,Hypsizygus ulmarius, Inonotus andersonii, Inonotus dryadeus, Inonotushispidus, Laetiporus cincinnatus, Laetiporus conifericola, Laetiporussulphureus, Lentinus ponderosus, Lenzites betulina, Lepiota procera(Macrolepiota procera), Lepiota rachodes (Chlorophyllum rachodes),Lepista nuda, Mycena alcalina, Mycena aurantiadisca, Mycena pura,Panaeolus foenisecii, Panaeolus subbalteatus, Panellus serotinus,Panellus serotinus, Panellus stipticus, Phellinus igniarius, Phellinuslinteus, Phellinus pini, Piptoporus betulinus, Pleurotus columbinus,Pleurotus cystidiosus, Pleurotus ostreatus, Pleurotus pulmonarius,Pleurotus sapidus, Pleurotus tuberregium, Pluteus cervinus, Polyporuselegans, Psathyrella aquatica, Psathyrella condolleana, Psathyrellahydrophila, Psilocybe allenii, Psilocybe azurescens, Psilocybecaerulescens, Psilocybe coprophila, Psilocybe cubensis, Psilocybecyanescens, Psilocybe ovoideocystidiata, Psilocybe stuntzii, Psilocybesubaeruginosa, Stereum complicatum, Stereum hirsutum, Stereum ostrea,Stropharia aeruginosa, Stropharia cyanea, Stropharia rugoso-annulata,Stropharia semiglobata, Stropharia semigloboides, Stropharia squamosa,Strophana thrausta, Stropharia umbonotescens, Termitomyces robusta,Trametes aesculi, Trametes cingulata, Trametes ectypa, Trametes elegans,Trametes gibbosa, Trametes hirsuta, Trametes ochracea, Trametespubescens, Trametes villosa, Volvaria bombycina, Volvarella volvacea,Wolfipora cocos, or combinations thereof. The above composition can alsocontain one or more adversive compounds as described herein.

Another embodiment is a composition of one or more tryptamines or inpure form or extracts from psilocybin containing mushrooms, orcombinations thereof combined with one or more extracts or purechemicals from plant species comprising one or more of Bacopa species(Bacopa monnien), Gotu kola (Centella asiatica), and Gingko (Gingkobiloba, Ginger (Zingiber officinale), Holy Basil (Ocimum sanctum), HuZhang (Polygonum cuspidatum), Oregano (Origanum vulgare, Origanumonites), Rosemary (Rosmarinus officinalis, Rosmarinus eriocalyx, speciesin the genus Rosmarinus), Turmeric (Curcuma longa), Green Tea (Camelliasinensis), lavender (Lavandula spica and related species in the genusLavandula), skullcap (Scutellaria lateriflora) oat straw (Avena sativa,Avena byzantina), Salvia divinorum, aka Diviner's Sage, Banisteropsiscaapi and Psychotria species, plants containing ibogaine (Tabemantheiboga, Voacanga africana and Tabemaemontana undulate), peyote(Lophophora williamsii), the seeds of morning glory (Ipomoea tricolorand related species) and Hawaiian baby wood rose (Argyreia nervosa),Acacia confusa, Acacia obtusifolia, Acacia simplicifolia, Desmanthusillinoensis, or Cannabis (Cannabis sativa, C. indica and C. ruderalis).The above composition can also contain one or more adversive compoundsas described herein.

Another embodiment is a composition of one or more tryptamines or inpure form or extracts from psilocybin containing mushrooms, orcombinations thereof combined with one or more monamine oxidase (MAO)inhibitors, such as β-carbolines (e.g., harmane, harmine, norharmine,perlolyrine, harmol, cordysinin, inter alia), to any of the abovementioned compositions to enhance the pharmaceutical efficacy of thetryptamine(s).

Pharmaceutical excipients useful for the compositions as describedherein comprise: acidifying agents (acetic acid, glacial acetic acid,citric acid, fumaric acid, hydrochloric acid, diluted hydrochloric acid,malic acid, nitric acid, phosphoric acid, diluted phosphoric acid,sulfuric acid, tartaric acid); alkalizing agents (ammonia solution,ammonium carbonate, diethanolamine, diisopropanolamine, potassiumhydroxide, sodium bicarbonate, sodium borate, sodium carbonate, sodiumhydroxide, trolamine); antifoaming agents (dimethicone, simethicone);antimicrobial preservatives (benzalkonium chloride, benzalkoniumchloride solution, benzethonium chloride, benzoic acid, benzyl alcohol,butylparaben, cetylpyridinium chloride, chlorobutanol, chlorocresol,cresol, dehydroacetic acid, ethylparaben, methylparaben, methylparabensodium, phenol, phenylethyl alcohol, phenylmercuric acetate,phenylmercuric nitrate, potassium benzoate, potassium sorbate,propylparaben, propylparaben sodium, sodium benzoate, sodiumdehydroacetate, sodium propionate, ascorbic acid, thimerosal, thymol);antioxidants (ascorbic acid, ascorbyl palmitate, butylatedhydroxyanisole, butylated hydroxytoluene, hypophosphorous acid,monothioglycerol, propyl gallate, sodium formaldehyde sulfoxylate,sodium metabisulfite, sodium thiosulfate, sulfur dioxide, tocopherol,tocopherols excipient); buffering agents (acetic acid, ammoniumcarbonate, ammonium phosphate, boric acid, citric acid, lactic acid,phosphoric acid, potassium citrate, potassium metaphosphate, potassiumphosphate monobasic, sodium acetate, sodium citrate, sodium lactatesolution, dibasic sodium phosphate, monobasic sodium phosphate);chelating agents (edetate disodium, ethylenediaminetetraacetic acid andsalts, edetic acid); coating agents (sodium carboxymethylcellulose,cellulose acetate, cellulose acetate phthalate, ethylcellulose, gelatin,pharmaceutical glaze, hydroxypropyl cellulose, hydroxypropylmethylcellulose, hydroxypropyl methylcellulose phthalate, methacrylicacid copolymer, methylcellulose, polyvinyl acetate phthalate, shellac,sucrose, titanium dioxide, carnauba wax, microcrystalline wax, zein);colorants (caramel, red, yellow, black or blends, ferric oxide);complexing agents (ethylenediaminetetraacetic acid and salts (EDTA),edetic acid, gentisic acid ethanolamide, oxyquinoline sulfate);desiccants (calcium chloride, calcium sulfate, silicon dioxide);emulsifying and/or solubilizing agents (acacia, cholesterol,diethanolamine (adjunct), glyceryl monostearate, lanolin alcohols, mono-and di-glycerides, monoethanolamine (adjunct), lecithin, oleic acid(adjunct), oleyl alcohol (stabilizer), poloxamer, polyoxyethylene 50stearate, polyoxyl 35 castor oil, polyoxyl 40 hydrogenated castor oil,polyoxyl 10 oleyl ether, polyoxyl 20 cetostearyl ether, polyoxyl 40stearate, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate80, diacetate, monostearate, sodium lauryl sulfate, sodium stearate,sorbitan monolaurate, sorbitan monooleate, sorbitan monopalmitate,sorbitan monostearate, stearic acid, trolamine, emulsifying wax);filtering aids (powdered cellulose, purified siliceous earth): flavorsand perfumes (anethole, benzaldehyde, ethyl vanillin, menthol, methylsalicylate, monosodium glutamate, orange flower oil, peppermint,peppermint oil, peppermint spirit, rose oil, stronger rose water,thymol, tolu balsam tincture, vanilla, vanilla tincture, vanillin);humectants (glycerol, hexylene glycol, sorbitol); plasticizers (e.g.,castor oil, diacetylated monoglycerides, diethyl phthalate, glycerol,mono- and di-acetylated monoglycerides, propylene glycol, triacetin,triethyl citrate); polymers (e.g., cellulose acetate, alkyl celluloses,hydroxyalkyl, acrylic polymers and copolymers); solvents (acetone,alcohol, diluted alcohol, amylene hydrate, benzyl benzoate, butylalcohol, carbon tetrachloride, chloroform, corn oil, cottonseed oil,ethyl acetate, glycerol, hexylene glycol, isopropyl alcohol, methylalcohol, methylene chloride, methyl isobutyl ketone, mineral oil, peanutoil, propylene carbonate, sesame oil, water for injection, sterile waterfor injection, sterile water for irrigation, purified water); sorbents(powdered cellulose, charcoal, purified siliceous earth); carbon dioxidesorbents (barium hydroxide lime, soda lime); stiffening agents(hydrogenated castor oil, cetostearyl alcohol, cetyl alcohol, cetylesters wax, hard fat, paraffin, polyethylene excipient, stearyl alcohol,emulsifying wax, white wax, yellow wax); suspending and/orviscosity-increasing agents (acacia, agar, alginic acid, aluminummonostearate, bentonite, purified bentonite, magma bentonite, carbomer,carboxymethylcellulose calcium, carboxymethylcellulose sodium,carboxymethylcellulose sodium carrageenan, microcrystalline andcarboxymethylcellulose sodium cellulose, dextrin, gelatin, guar gum,hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethylcellulose, magnesium aluminum silicate, methylcellulose, pectin,polyethylene oxide, polyvinyl alcohol, povidone, alginate, silicondioxide, colloidal silicon dioxide, sodium alginate, tragacanth, xanthangum); sweetening agents (aspartame, dextrates, dextrose, excipientdextrose, fructose, mannitol, saccharin, calcium saccharin, sodiumsaccharin, sorbitol, solution sorbitol, sucrose, compressible sugar,confectioner's sugar, syrup); surfactants (simethicone); tablet binders(acacia, alginic acid, sodium carboxymethylcellulose, microcrystallinecellulose, dextrin, ethylcellulose, gelatin, liquid glucose, guar gum,hydroxypropyl methylcellulose, methylcellulose, polyethylene oxide,povidone, pregelatinized starch, syrup); tablet and/or capsule diluents(calcium carbonate, dibasic calcium phosphate, tribasic calciumphosphate, calcium sulfate, microcrystalline cellulose, powderedcellulose, dextrates, dextrin, dextrose excipient, fructose, kaolin,lactose, mannitol, sorbitol, starch, pregelatinized starch, sucrose,compressible sugar, confectioner's sugar); tablet disintegrants (alginicacid, microcrystalline cellulose, croscarmellose sodium, crospovidone,polacrilin potassium, sodium starch glycolate, starch, pregelatinizedstarch); tablet and/or capsule lubricants (calcium stearate, glycerylbehenate, magnesium stearate, light mineral oil, sodium stearylfumarate, stearic acid, purified stearic acid, talc, hydrogenatedvegetable oil, zinc stearate); thickening agents (gelatin having a bloomstrength of 50-100); tonicity agent (dextrose, glycerol, mannitol,potassium chloride, sodium chloride); vehicle: flavored and/or sweetened(aromatic elixir, compound benzaldehyde elixir, iso-alcoholic elixir,peppermint water, sorbitol solution, syrup, tolu balsam syrup); vehicle:oleaginous (almond oil, corn oil, cottonseed oil, ethyl oleate,isopropyl myristate, isopropyl palmitate, mineral oil, light mineraloil, myristyl alcohol, octyl dodecanol, olive oil, peanut oil, persicoil, sesame oil, soybean oil, squalane); vehicle: solid carrier (sugarspheres); vehicle: sterile (bacteriostatic water for injection,bacteriostatic sodium chloride injection); viscosity-increasing (seesuspending agent); water repelling agents (cyclomethicone, dimethicone,simethicone); and/or solubilizing agent (benzalkonium chloride,benzethonium chloride, cetylpyridinium chloride, docusate sodium,nonoxynol 9, nonoxynol 10, octoxynol 9, poloxamer, polyoxyl 35 castoroil, polyoxyl 40, hydrogenated castor oil, polyoxyl 50 stearate,polyoxyl 10 oleyl ether, polyoxyl 20, cetostearyl ether, polyoxyl 40stearate, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate80, sodium lauryl sulfate, sorbitan monolaurate, sorbitan monooleate,sorbitan monopalmitate, sorbitan monostearate, tyloxapol). This list isnot meant to be exclusive, but instead merely representative of theclasses of excipients and the particular excipients that may be used inoral dosage forms as described herein. See Remington's Essentials ofPharmaceutics, Pharmaceutical Press Publishing Company, London, UK,1^(st) Edition, 2013, and the Handbook of Pharmaceutical Excipients,8^(th) Edition, Pharmaceutical Press Publishing Company London, U K,2017, each of which is incorporated by reference herein for suchteachings.

Another embodiment is a method for manufacturing a dosage formcomprising formulating a composition as described herein comprisingsprays, capsules, tablets, elixirs, emulsions, lozenges, suspensions,syrups, pills, lotions, epidermal patches, suppositories, inhalers, orinjectables. Any methods known to the art for formulating extracts oractive principal ingredients into lotions, soaps, etc. may be utilized.

In one embodiment, the pharmaceutical composition comprises a dose ofabout 1 ng to about 10 mg of one or more tryptamines or an amount of amushroom (or plant) extract or mushroom (or plant) having an equivalentamount of tryptamine(s). In another embodiment, the compositioncomprises about 1 μg to about 100 μg of one or more tryptamines or anamount of a mushroom extract or mushroom having an equivalent amount oftryptamine(s). In another embodiment, the composition comprises about 1μg to about 5 mg of one or more tryptamines or an amount of a mushroomextract or mushroom having an equivalent amount of tryptamine(s).

In another embodiment, the composition comprises about 100 μg to about 1mg of one or more tryptamines or an amount of a mushroom extract ormushroom having an equivalent amount of tryptamine(s). In one aspect,the composition comprises about: 1 μg, 5 μg. 10 μg, 20 μg, 30 μg. 40 μg,50 μg, 60 μg, 70 μg, 80 μg, 90 μg, 100 μg, 110 μg, 120 μg, 130 μg, 140μg, 150 μg, 160 μg, 170 μg, 180 μg, 190 μg, 200 μg, 210 μg, 220 μg, 230μg, 240 μg, 250 μg, 260 μg, 270 μg, 280 μg, 290 μg, 300 μg, 310 μg, 320μg, 330 μg, 340 μg, 350 μg, 360 μg, 370 μg, 380 μg, 390 μg. 400 μg, 410μg, 420 μg, 430 μg, 440 μg. 450 μg, 460 μg, 470 μg, 480 μg, 490 μg. 500μg, 510 μg, 520 μg, 530 μg, 540 μg, 550 μg, 560 μg, 570 μg, 580 μg, 590μg, 600 μg. 610 μg, 620 μg, 630 μg 640 μg, 650 μg, 660 μg, 670 μg, 680μg, 690 μg, 700 μg, 710 μg 720 μg 730 μg, 740 μg, 750 μg. 760 μg, 770μg, 780 μg. 790 μg, 800 μg, 810 μg, 820 μg. 830 μg, 840 μg, 850 μg, 860μg. 870 μg, 880 μg, 890 μg. 900 μg, 910 μg. 920 μg, 930 μg. 940 μg, 950μg, 960 μg. 970 μg. 980 μg, 990 μg, or 1000 μg of one or moretryptamines or an amount of a mushroom extract or mushroom having anequivalent amount of tryptamine(s). In another aspect, the compositioncomprises about 0.1 mg, 0.2 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg,0.8 mg, 0.9 mg, 1.0 mg, 1.1 mg, 1.2 mg, 1.3 mg, 1.4 mg, 1.5 mg, 1.6 mg,1.7 mg, 1.8 mg, 1.9 mg 2.0 mg, 2.1 mg, 2.2 mg, 2.3 mg, 2.4 mg, 2.5 mg,2.6 mg, 2.7 mg, 2.8 mg, 2.9 mg, 3.0 mg, 3.1 mg, 3.2 mg, 3.3 mg, 3.4 mg,3.5 mg, 3.6 mg, 3.7 mg, 3.8 mg, 3.9 mg, 4.0 mg, 4.1 mg, 4.2 mg, 4.3 mg,4.4 mg, 4.5 mg, 4.6 mg, 4.7 mg, 4.8 mg, 4.9 mg, 5.0 mg, 5.1 mg, 5.2 mg,5.3 mg, 5.4 mg, 5.5 mg, 5.6 mg, 5.7 mg, 5.8 mg, 5.9 mg, 6.0 mg, 6.1 mg,6.2 mg, 6.3 mg. 6.4 mg, 6.5 mg, 6.6 mg, 6.7 mg, 6.8 mg, 6.9 mg, 7.0 mg,7.1 mg, 7.2 mg, 7.3 mg, 7.4 mg, 7.5 mg, 7.6 mg, 7.7 mg, 7.8 mg, 7.9 mg,8.0 mg, 8.1 mg, 8.2 mg, 8.3 mg, 8.4 mg, 8.5 mg, 8.6 mg, 8.7 mg, 8.8 mg,8.9 mg, 9.0 mg, 9.1 mg, 9.2 mg, 9.3 mg, 9.4 mg, 9.5 mg, 9.6 mg, 9.7 mg,9.8 mg, 9.9 mg, or 10.0 mg of one or more tryptamines or an amount of amushroom extract or mushroom having an equivalent amount oftryptamine(s).

The percent mass of psilocybin, psilocin, and baeocystin in driedPsilocybe mushrooms is shown in Table 2.

TABLE 2 Psilocybin, psilocin, and baeocystin concentrations in psilocybemushrooms Mass percent based on dry weight of mushroom SpeciesPsilocybin Psilocin Baeocystin P. azurescens 1.78 0.38 0.35 P. bohemica1.34 0.11 0.02 P. semilanceata 0.98 0.02 0.36 P. baeocystis 0.85 0.590.10 P. cyanescens 0.85 0.36 0.03 P. tampanensis 0.68 0.32 n/d P.cubensis 0.63 0.60 0.025 P. weilii 0.61 0.27 0.05 P. hoogshagenii 0.600.10 n/d P. stuntzii 0.36 0.12 0.02 P. cyanofibrillosa 0.21 0.04 n/d P.liniformans 0.16 n/d 0.05 Average 0.754% 0.243% 0.137% Data fromStamets, Psilocybin Mushrooms of the World, Ten Speed Press, page 39(1996)

Table 3 shows the relative amount of psilocybin, psilocin, andbaeocystin in dried Psilocybe mushrooms.

TABLE 3 Relative amounts of psilocybin, psilocin, baeocystin in dryPsilocybe mushrooms Psilocybin Psilocin Baeocystin Dry Mushroom 0.754%0.243% 0.137% g mg mg mg 0.2-0.8 1.5-6.0 0.5-1.9 0.3-1.1 0.8-1.0 6.0-7.51.9-2.4 1.1-1.4 1.0-1.5  7.5-11.3 2.4-3.6 1.4-2.1 1.5-3.0 11.3-22.63.6-7.3 2.1-4.1 3.0-4.0 22.6-30.2 7.3-9.7 4.1-5.5 4.0-5.0 30.2-37.7 9.7-12.2 5.5-6.9 Based on data from Stemets, Psilocybin Mushrooms ofthe World, Ten Speed Press, page 39 (1996)

In one embodiment, the dose of tryptamine is about 0.00001 mg/kg toabout 0.2 mg/kg, assuming an average mass of 70 kg for a human. In oneembodiment, the dose of tryptamine is 0.0001 mg/kg to about 0.001 mg/kg.In another embodiment, the dose of tryptamine is 0.001 mg/kg to about0.01 mg/kg. In another embodiment, the dose of tryptamine is 0.01 mg/kgto about 0.1 mg/kg. In another embodiment, the dose of tryptamine is 0.1mg/kg to about 0.2 mg/kg. In another embodiment, the dose of tryptamineis about 0.005 mg/kg, 0.01 mg/kg, 0.02 mg/kg, 0.03 mg/kg, 0.04 mg/kg,0.05 mg/kg, 0.06 mg/kg, 0.07 mg/kg, 0.08 mg/kg, 0.09 mg/kg, 0.10 mg/kg,0.11 mg/kg, 0.12 mg/kg, 0.13 mg/kg, 0.14 mg/kg, 0.15 mg/kg, 0.16 mg/kg,0.17 mg/kg, 0.18 mg/kg, 0.19 mg/kg, 0.20 mg/kg, In another embodiment,the dose of tryptamine is about 0.01 mg/kg to about 0.05 mg/kg. Inanother embodiment, the dose of tryptamine is about 0.01 mg/kg to about0.02 mg/kg.

In one embodiment, the dose of the phenethylamines, amphetamines,erinacines, hericenones, cannabinoids one or more adversive compoundssuch as niacin, capsaicin, ipecac, apomorphine, bittering agents, or anamount of a mushroom or plant extract or mushroom or plant having anequivalent amount of about 1 ng, 5 ng, 10 ng, 20 ng, 30 ng, 40 ng, 50ng, 60 ng, 70 ng, 80 ng, 90 ng, 100 ng, 110 ng, 120 ng, 130 ng, 140 ng,150 ng, 160 ng, 170 ng, 180 ng, 190 ng, 200 ng, 210 ng, 220 ng, 230 ng,240 ng, 250 ng, 260 ng, 270 ng, 280 ng, 290 ng, 300 ng, 310 ng, 320 ng,330 ng, 340 ng, 350 ng, 360 ng, 370 ng, 380 ng, 390 ng, 400 ng, 410 ng,420 ng, 430 ng, 440 ng, 450 ng, 460 ng, 470 ng, 480 ng, 490 ng, 500 ng,510 ng, 520 ng, 530 ng, 540 ng, 550 ng, 560 ng, 570 ng, 580 ng, 590 ng,600 ng, 610 ng, 620 ng, 630 ng, 640 ng, 650 ng, 660 ng, 670 ng, 680 ng,690 ng, 700 ng, 710 ng, 720 ng, 730 ng, 740 ng, 750 ng, 760 ng, 770 ng,780 ng, 790 ng, 800 ng, 810 ng, 820 ng, 830 ng, 840 ng, 850 ng, 860 ng,870 ng, 880 ng, 890 ng, 900 ng, 910 ng, 920 ng, 930 ng, 940 ng, 950 ng,960 ng, 970 ng, 980 ng, 990 ng, or 1000 ng; 1 μg, 5 μg, 10 μg, 20 μg, 30μg, 40 μg, 50 μg, 60 μg, 70 μg, 80 μg, 90 μg, 100 μg, 110 μg, 120 μg,130 μg, 140 μg, 150 μg. 160 μg, 170 μg, 180 μg. 190 μg, 200 μg, 210 μg,220 μg. 230 μg, 240 μg, 250 μg, 260 μg, 270 μg, 280 μg, 290 μg, 300 μg,310 μg. 320 μg, 330 μg, 340 μg, 350 μg, 360 μg, 370 μg, 380 μg, 390 μg,400 μg, 410 μg, 420 μg, 430 μg, 440 μg, 450 μg, 460 μg, 470 μg, 480 μg.490 μg, 500 μg, 510 μg, 520 μg, 530 μg, 540 μg, 550 μg, 560 μg, 570 μg,580 μg, 590 μg, 600 μg, 610 μg, 620 μg, 630 μg, 640 μg, 650 μg, 660 μg.670 μg, 680 μg, 690 μg. 700 μg, 710 μg. 720 μg, 730 μg, 740 μg, 750 μg,760 μg. 770 μg, 780 μg, 790 μg, 800 μg, 810 μg, 820 μg, 830 μg, 840 μg,850 μg, 860 μg, 870 μg, 880 μg, 890 μg, 900 μg, 910 μg, 920 μg, 930 μg,940 μg, 950 μg, 960 μg, 970 μg, 980 μg, 990 μg, or 1000 μg; 0.1 mg, 0.2mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg, 0.9 mg, 1.0 mg, 1.1mg, 1.2 mg, 1.3 mg, 1.4 mg, 1.5 mg, 1.6 mg, 1.7 mg, 1.8 mg, 1.9 mg, 2.0mg, 2.1 mg, 2.2 mg, 2.3 mg, 2.4 mg, 2.5 mg, 2.6 mg, 2.7 mg, 2.8 mg, 2.9mg, 3.0 mg, 3.1 mg, 3.2 mg, 3.3 mg, 3.4 mg, 3.5 mg, 3.6 mg, 3.7 mg, 3.8mg, 3.9 mg, 4.0 mg, 4.1 mg, 4.2 mg, 4.3 mg, 4.4 mg, 4.5 mg, 4.6 mg, 4.7mg, 4.8 mg, 4.9 mg, 5.0 mg, 5.1 mg, 5.2 mg, 5.3 mg, 5.4 mg, 5.5 mg, 5.6mg, 5.7 mg, 5.8 mg, 5.9 mg, 6.0 mg, 6.1 mg, 6.2 mg, 6.3 mg, 6.4 mg, 6.5mg, 6.6 mg, 6.7 mg, 6.8 mg, 6.9 mg, 7.0 mg, 7.1 mg, 7.2 mg, 7.3 mg, 7.4mg, 7.5 mg, 7.6 mg, 7.7 mg, 7.8 mg, 7.9 mg, 8.0 mg, 8.1 mg, 8.2 mg, 8.3mg, 8.4 mg, 8.5 mg, 8.6 mg, 8.7 mg, 8.8 mg, 8.9 mg, 9.0 mg, 9.1 mg, 9.2mg, 9.3 mg, 9.4 mg, 9.5 mg, 9.6 mg, 9.7 mg, 9.8 mg, 9.9 mg, or 10.0 mg;0.1 mg, 0.25 mg, 0.5 mg, 1.0 mg, 2.5 mg, 5.0 mg, 10.0 mg, 20.0 mg, 30.0mg, 40.0 mg, 50.0 mg, 60.0 mg, 70.0 mg, 80.0 mg, 90.0 mg, or 100.0 mg; 1mg, 5 mg, 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, 125 mg, 150 mg, 175 mg,200 mg, 225 mg, 250 mg, 275 mg, 300 mg, 325 mg, 350 mg, 375 mg, 400 mg,425 mg, 450 mg, 475 mg, or 500 mg of compound.

In one embodiment, the dose of the phenethylamines, amphetamines,erinacines, hericenones, cannabinoids one or more adversive compoundssuch as niacin, capsaicin, ipecac, apomorphine, bittering agents, or anamount of a mushroom or plant extract or mushroom or plant having anequivalent amount of about 0.1 mg/kg, 0.25 mg/kg, 0.5 mg/kg, 0.75 mg/kg,1 mg/kg, 2.5 mg/kg, 5 mg/kg, 10 mg/kg, 15 mg/kg, 20 mg/kg, 25 mg/kg, 30mg/kg, 35 mg/kg, 40 mg/kg, 45 mg/kg, 50 mg/kg, 55 mg/kg, 60 mg/kg, 65mg/kg, 70 mg/kg, 75 mg/kg, 80 mg/kg, 85 mg/kg, 90 mg/kg, 95 mg/kg, or100 mg/kg.

In one embodiment, the pharmaceutical composition comprises:

-   0.001 mg to 0.01 mg, 0.01 mg to 0.1 mg, 0.01 mg to 1 mg, 0.1 mg to 5    mg, 0.1 mg to 1 mg, 0.5 mg to 1 mg, 0.5 mg to 5 mg, 0.25 mg to 1 mg,    0.2 mg to 2 mg, 0.2 mg to 5 mg of one or more tryptamines or an    amount of a plant or mushroom extract or plant or mushroom to    provide an equivalent dose; and/or-   0.1 mg to 1 mg, 1 mg to 10 mg, 10 mg to 100 mg, 10 mg to 50 mg, 50    mg to 100 mg, 20 mg to 80 mg, 20 mg to 50 mg, 50 mg to 100 mg, 50 mg    to 80 mg, 10 mg to 80 mg phenethylamines or amphetamines or an    amount of a plant or mushroom extract or plant or mushroom to    provide an equivalent dose; and/or-   1 μg to 5 μg, 1 μg to 10 μg, 5 μg to 10 μg, 10 μg to 5 mg, 10 μg to    100 μg, 100 μg to 1 mg, 500 μg to 1 mg, 500 μg to 5 mg, 1 mg to 5    mg, 100 μg to 1 mg, 100 μg to 500 μg, 100 μg to 250 μg; 250 μg to 1    mg; 750 μg to 1 mg, 250 μg to 750 μg, erinacines or hericenones or    an amount of a plant or mushroom extract or plant or mushroom to    provide an equivalent dose; and/or-   0.01 mg to 0.1 mg, 0.01 mg to 1 mg, 0.1 mg to 10 mg, 0.1 mg to 1 mg,    0.5 mg to 1 mg, 0.5 mg to 5 mg, 0.25 mg to 1 mg, 0.2 mg to 2 mg, 0.2    mg to 5 mg, 1 mg to 10 mg cannabinoids or an amount of a plant    extract or plant or mushroom to provide an equivalent dose; and/or-   0.1 mg to 10 mg, 1 mg to 500 mg, 1 mg to 100 mg, 200 mg to 500 mg,    50 mg to 200 mg, 10 mg to 50 mg, 50 mg to 200 mg, 1 mg to 200 mg, 1    mg to 50 mg of adversive.

In one embodiment, the pharmaceutical compositions described hereinprovide a dosage form of the pharmaceutical compositions described herefor administration to a subject. In one embodiment, the subject issuffering from or has the symptoms of one or more neurologic diseases ordisorders or wishes to enhance one or more cognitive or sensory motortraits. The dosage form can be administered, for example, to a subject,or a subject in need thereof. In one aspect, the subject is a mammal, ora mammal in need thereof. In one aspect, the subject is a human, orhuman in need thereof. In one aspect, the subject is a human or a humanin need thereof. In one aspect, the subject is a child (˜0-9 years old)or an adolescent (˜10-17 years old). In one aspect, the subject is fromabout 0 to about 9 years of age. In another aspect, the subject is fromabout 10 years to about 17 years of age. In another aspect, the subjectis over 17 years of age. In another aspect, the subject is an adult (≥18years of age).

One or more dosage forms of the compositions described herein can beadministered, for example, 1×, 2×, 3×, 4×, 5×, 6×, or even more timesper day. One or more dosage forms can be administered, for example, for1, 2, 3, 4, 5, 6, 7 days, or even longer. One or more dosage forms canbe administered, for example, for 1, 2, 3, 4 weeks, or even longer. Oneor more dosage forms can be administered, for example, for 1, 2, 3, 4,5, 6, 7, 8, 9, 10, 11, 12 months, 1 year, 2, years, 3 years, 4 years, 5years, over 5 years, a decade, multiple decades, or even longer. One ormore dosage forms can be administered at a regular interval until thesubject or subject in need thereof, does not require treatment,prophylaxis, or amelioration of any disease or condition including butnot limited to a neurological or neurodegenerative disease or disorder.

In one embodiment, the compositions described herein can be administeredas dosage forms in various regimens, including one dose per day (QD),two doses per day (BID), three doses per day (TID), or four times perday (QID) to achieve a total daily dosage. In another embodiment, any ofthe foregoing doses comprise a total daily dosage.

Another embodiment described herein is a method of treating a subjectsuffering from or having the symptoms of a neurological orneurodegenerative disease or disorder by orally administering one ormore of the pharmaceutical compositions described herein to the subject.The composition may be administered in one or more doses, one or moretimes per day for a total daily dosage.

In one aspect, the compositions described herein are effective to atleast partially treat, alleviate, prevent or ameliorate serotonin(5-hydroxytryptamine, 5-HT) receptor disorders, psychiatric, or mooddisorders, e.g., depression, anxiety, major depressive disorder,treatment resistant depression, persistent depression, manic depressionor bipolar disorder, depressive psychosis, perinatal depression,premenstrual dysphoric disorder, seasonal depressions, situationaldepression, panic disorder, obsessive compulsive disorder,post-traumatic stress disorder, attention deficit/hyperactivitydisorder, sleep disorders, eating disorders, schizophrenia, personalitydisorders, substance abuse disorders (drug abuse, addiction,alcoholism); neuronal injuries or physical neurodegeneration (e.g.,physical injury, head trauma, spinal cord trauma, concussion, peripheralneuron trauma, paralysis, ischemia, hypoxia, stroke; organophosphates,lead, heavy metals, nerve agents, other toxic compounds, prions, amyloidplaque, neurotoxic viruses, stress); neurodegenerative diseases (e.g.,Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis,multiple sclerosis, frontotemporal dementia, Huntington's disease,adrenal leukodystrophy, Alexander's disease, Alper's disease,Alzheimer's disease, amyotrophic lateral sclerosis, balo concentricsclerosis, Canavan disease, Charcot-Marie-Tooth disease, childhoodataxia with central nervous system hypomyelination, chronic idiopathicperipheral neuropathy, frontotemporal dementia, Huntington's disease,Krabbe disease, monomelic amyotrophy, multiple sclerosis (MS),neurodegeneration, neuromyelitis optica, neuropathic pain,neurosarcoidosis, Parkinson's disease, Pelizaeus-Merzbacher disease,primary lateral sclerosis, progressive supranuclear palsy, radicularpain, radiculopathic pain, Schilder's disease, sciatic pain, sciatica,subacute necrotizing myelopathy, transverse myelitis, or Zellwegersyndrome); congenital or organic cognitive impairment, learningdisabilities, autism spectrum disorder; cognitive enhancement,intelligence enhancement, creativity enhancement, memory improvement,learning enhancement and improvement, spiritual enhancement, “mindexpansion,” IQ improvement, EQ improvement, balance enhancement,athleticism, motor skill enhancement, special navigation, clairvoyance,psychic enhancement, or general improvement of mental health.

One embodiment described herein is a composition comprising one or moreof a tryptamine, a phenethylamine, an amphetamine, an erinacine, ahericenone, a cannabinoid, or a pharmaceutically acceptable salt,hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, or acombination thereof, and a pharmaceutically acceptable carrier, for usein treating neuronal injuries, neurodegeneration, neurological diseases,congenital or organic cognitive impairment, learning disabilities,autism spectrum disorder, psychiatric and mood disorders, cognitiveenhancement, physical or motor neuron enhancement, or generalimprovement of mental health in a subject in need thereof.

Another embodiment described herein is a method of treating, preventing,ameliorating or reducing the symptoms of serotonin (5-hydroxytryptamine,5-HT) receptor disorders, neuronal injuries, neurodegeneration,neurological diseases, congenital or organic cognitive impairment,learning disabilities, autism spectrum disorder, psychiatric and mooddisorders, cognitive enhancement, physical or motor neuron enhancement,or general improvement of mental health in a subject in need thereof byadministering a composition comprising one or more of a tryptamine, aphenethylamine, an amphetamine, an erinacine, a hericenone, acannabinoid, or a pharmaceutically acceptable salt, hydrate, solvate,prodrug, stereoisomer, or tautomer thereof, or a combination thereof,and a pharmaceutically acceptable carrier.

In one embodiment, the tryptamine comprises psilocybin, baeocystin,norbaeocystin, psilocin, norpsilocin, 4-hydroxytryptamine,N,N-dimethyltryptamine, 5-hydroxytryptamine (serotonin), tryptamine,aeruginascin, 4-hydroxy-N,N,N-trimethyltryptamine,5-hydroxy-N,N,N-trimethyltryptamine (bufotenidine), N-methyltryptamine,N-ethyltryptamine, N-methyl-N-ethyltryptamine,N-methyl-N-propyltryptamine, N,N-diethyltryptamine,N-methyl-N-isopropyltryptamine, N-ethyl-N-isopropyltryptamine,N,N-diisopropyltryptamine, N,N-dipropyltryptamine,N,N-dipropyltryptamine, N,N-diallyltryptamine, 4-hydroxytryptamine,4-hydroxy-N-methyltryptamine (norpsilocin),4-hydroxy-N,N-dimethyltryptamine (psilocin),4-hydroxy-N-methyl-N-ethyltryptamine,4-hydroxy-N-methyl-N-propyltryptamine, 4-hydroxy-N,N-diethyltryptamine,4-hydroxy-N,N-diethyltryptamine,4-hydroxy-N-ethyl-N-isopropyltryptamine,4-hydroxy-N,N-diisopropyltryptamine, 4-hydroxy-N,N-dipropyltryptamine,4-hydroxy-N—N-dipropyltryptamine, 4-hydroxy-N,N-diallyltryptamine,4-methoxytryptamine, 4-methoxy-N-methyltryptamine (norpsilocin),4-methoxy-N,N-dimethyltryptamine (psilocin),4-methoxy-N-methyl-N-ethyltryptamine,4-methoxy-N-methyl-N-propyltryptamine, 4-methoxy-N,N-diethyltryptamine,4-methoxy-N,N-diethyltryptamine,4-methoxy-N-ethyl-N-isopropyltryptamine,4-methoxy-N,N-diisopropyltryptamine, 4-methoxy-N,N-dipropyltryptamine,4-methoxy-N—N-dipropyltryptamine, 4-methoxy-N—N-diallyltryptamine,4-acetoxytryptamine, 4-acetoxy-N-methyltryptamine,4-acetoxy-N-methyl-N-ethyltryptamine,4-acetoxy-N-methyl-N-ethyltryptamine,4-acetoxy-N-methyl-N-propyltryptamine, 4-acetoxy-N,N-diethyltryptamine,4-acetoxy-N-methyl-N-isopropyltryptamine,4-acetoxy-N-ethyl-N-isopropyltryptamine,4-acetoxy-N,N-diisopropyltryptamine, 4-acetoxy-N,N-dipropyltryptamine,4-acetoxy-N—N-dipropyltryptamine, 4-acetoxy-N—N-diallyltryptamine,5-hydroxytryptamine, 5-hydroxy-N-methyltryptamine,5-hydroxy-N,N-dimethyltryptamine (bufotenine),5-hydroxy-N-methyl-N-ethyltryptamine,5-hydroxy-N-methyl-N-propyltryptamine, 5-hydroxy-N,N-diethyltryptamine,5-hydroxy-N-methyl-N-isopropyltryptamine,5-hydroxy-N-ethyl-N-isopropyltryptamine,5-hydroxy-N,N-diisopropyltryptamine, 5-hydroxy-N,N-dipropyltryptamine,5-hydroxy-N—N-dipropyltryptamine, 5-hydroxy-N—N-diallyltryptamine,5-methoxytryptamine, 5-methoxy-N-methyltryptamine,5-methoxy-N,N-dimethyltryptamine, 5-methoxy-N-methyl-N-ethyltryptamine,5-methoxy-N-methyl-N-propyltryptamine, 5-methoxy-N,N-diethyltryptamine,5-methoxy-N-methyl-N-isopropyltryptamine,5-methoxy-N-ethyl-N-isopropyltryptamine,5-methoxy-N,N-diisopropyltryptamine, 5-methoxy-N,N-dipropyltryptamine,5-methoxy-N—N-dipropyltryptamine, 5-methoxy-N—N-diallyltryptamine,5-acetoxytryptamine, 5-acetoxy-N-methyltryptamine,5-acetoxy-N,N-dimethyltryptamine, 5-acetoxy-N-methyl-N-ethyltryptamine,5-methoxy-N-methyl-N-propyltryptamine, 5-acetoxy-N,N-diethyltryptamine,5-acetoxy-N-methyl-N-isopropyltryptamine,5-acetoxy-N-ethyl-N-isopropyltryptamine,5-acetoxy-N,N-diisopropyltryptamine, 5-acetoxy-N,N-dipropyltryptamine,5-acetoxy-N—N-dipropyltryptamine, 5-acetoxy-N—N-diallyltryptamine,α-methyltryptamine, N-ethyl-N-isopropyltryptamine,N-methyl-N-butyltryptamine, 2,α-dimethyltryptamine,α-N-dimethyltryptamine, α-methyl-N,N-dimethyltryptamine,α-ethyltryptamine, 2-methyl-N,N-dimethyltryptamine,2-methyl-N,N-diethyltryptamine, 1-methylpsilocin,5-methoxy-α-methyltryptamine, ibogaine, harmaline,7-methoxy-1-methyl-1,2,3,4-tetrahydro-b-carboline (tetrahydroharmine),N,N-diethyl-D-lysergamide (LSD), 6-ally-N,N-diethyl-norlysergic acid(6-allyl-N,N-diethyl-norlysergic acid),9,10-didehydro-N,N,6-triethylergoline-8b-carboxamide(6,N,N-triethyl-norlysergic acid),9,10-didehydro-6-propyl-N,N-diethylergoline-8b-carboxamide(6-propyl-norlysergic acid), other tryptamine compounds, or apharmaceutically acceptable salt, hydrate, solvate, prodrug,stereoisomer, or tautomer thereof, or a combination thereof.

In another embodiment, the tryptamine comprises:6-Allyl-N,N-diethyl-norlysergic acid (AL-LAD), N,N-dibutyl-tryptamine(DBT), N,N-diethyl-tryptamine (DET), N,N-diisopropyl-tryptamine (DiPT),5-methyoxy-α-methyl-tryptamine (α,O-DMS), N,N-dimethyl-tryptamine (DMT),2,α-dimethyl-tryptamine (2,α-DMT), α,N-dimethyl-tryptamine (α,N-DMT),N,N-dipropyl-tryptamine (DPT), N-ethyl-N-isopropyl-tryptamine (EiPT),α-ethyl-tryptamine (AET), 6,N,N-tryptamineriethyl-norlysergic acid(ETH-LAD), 3,4-dihydro-7-methoxy-1-methyl-carboline (Harmaline),7-methyoxy-1-methyl-carboline (Harmine),N,N-dibutyl-4-hydroxy-tryptamine (4-HO-DBT),N,N-diethyl-4-hydroxy-tryptamine (4-HO-DET),N,N-diisopropyl-4-hydroxy-tryptamine (4-HO-DiPT),N,N-dimethyl-4-hydroxy-tryptamine (4-HO-DMT),N,N-dimethyl-5-hydroxy-tryptamine (5-HO-DMT),N,N-dipropyl-4-hydroxy-tryptamine (4-HO-DPT),N-ethyl-4-hydroxy-N-methyl-tryptamine (4-HO-MET),4-hydroxy-N-isopropyl-N-methyl-tryptamine (4-HO-MiPT),4-hydroxy-N-methyl-N-propyltryptamine (4-HO-MPT),4-hydroxy-N,N-tetramethylene-tryptamine (4-HO-pyr-tryptamine),12-methoxyibogamine (Ibogaine), N,N-diethyl-lysergic acid (LSD),N-butyl-N-methyl-tryptamine (MBT),N,N-diisopropyl-4,5-methylenedioxy-tryptamine (4,5-MDO-DiPT),N,N-diisopropyl-5,6-methylenedioxy-tryptamine (5,6-MDO-DiPT),N,N-dimethyl-4,5-methylenedioxy-tryptamine (4,5-MDO-DMT),N,N-dimethyl-5,6-methylenedioxy-tryptamine (5,6-MDO-DMT),N-isopropyl-N-methyl-5,6-methylenedioxy-tryptamine (5,6-MDO-MiPT),N,N-diethyl-2-methyl-tryptamine (2-Me-DET),2,N,N-tryptaminerimethyl-tryptamine (2-Me-DMT),N-acetyl-5-methoxy-tryptamine (melatonin),N,N-diethyl-5-methoxy-tryptamine (5-MeO-DET),N,N-diisopropyl-5-methoxy-tryptamine (5-MeO-DiPT),5-methoxy-N,N-dimethyl-tryptamine (5-MeO-DMT),N-isopropyl-4-methoxy-N-methyl-tryptamine (4-MeO-MiPT),N-isopropyl-5-methoxy-N-methyl-tryptamine (5-MeO-MiPT),5,6-dimethoxy-N-isopropyl-N-methyl-tryptamine (5,6-MeO-MiPT),5-methoxy-N-methyl-tryptamine (5-MeO-NMT),5-methoxy-N,N-tetramethylene-tryptamine (5-MeO-pyr-tryptamine),6-methoxy-1-methyl-1,2,3,4-tetrahydro-carboline (6-MeO-tryptamineHH),5-methoxy-2,N,N-trimethyl-tryptamine (5-MeO-tryptamineMT),N,N-dimethyl-5-methylthio-tryptamine (5-MeS-DMT),N-isopropyl-N-methyl-tryptamine (MiPT), α-methyl-tryptamine (α-MT),N-ethyl-tryptamine (NET), N-methyl-tryptamine (NMT),6-propyl-norlysergic acid (PRO-LAD), N,N-tetramethylene-tryptamine(pyr-T), Tryptamine (T), 7-methoxy-1-methyl-1,2,3,4-tetrahydro-carboline(Tetrahydroharmine), or α,N-dimethyl-5-methoxy-tryptamine (α,N,O-TMS),or a pharmaceutically acceptable salt, hydrate, solvate, prodrug,stereoisomer, or tautomer thereof, or a combination thereof. See Shulginand Shulgin, TIHKAL: The Continuation, Transform Press (1997), which isincorporated by reference herein for the specific teachings thereof.

In one embodiment, the tryptamine comprises a compound having thestructure of Formula 1,

-   wherein-   R₁ is H, OH, COOH, OCH₃, O(CH₂)_(n)CH₃, (CH₂)_(n)OH, (CH₂)_(n)COOH,    —C(O)CH₃, (CH₂)_(n)OC(O)N(R₆)₂, —(CH₂)_(n)C(O)OC(O)OH, PO₄, P₂O₇,    P₃O₁₀, SO₄, S₂O₇, S₃O₁₀, CHO₃, a C₁-C₆ mono-di-, or tri-carboxylic    acid, a pentose sugar, a hexose sugar, or an amino acid;-   R₂ is (CH₂)_(n)N(R₆)₂, (CH₂)_(n)O(R₆), or C₁-C₅ alkyl-N(R₇)₂:-   R₄ is H, CH₃, OH, CHOCH₃, or (CH₂)_(n)OH;-   R₅ is H, CH₃, OH, CHOCH₃, or (CH₂)_(n)CH₃;-   R₆ is H, CH₃, C₁-C₄ alkyl, OH, CHOCH₃, (CH₂)_(n)OH, OCH₃,    O(CH₂)_(n)CH₃.-   R⁷ is independently H, CH₃, C₁-C₄ alkyl, C₁-C₄ allyl, C₁-C₄ ethynyl,    OH, COOH, (CH₂)_(n)COOH; OCH₃, O(CH₂)_(n)CH₃, (CH₂)_(n)OH,    (CH₂)_(n)NH₂; dimethyl amine, pyrrole, pyrazole, imidazole,    pyridine, piperdine, pyridine, pyrimidine, indole, purine,    quinoline, morpholino, pyran, or furan;-   where n is 0, 1, 2, 3, or 4; and-   wherein-   mono-, di-, and tri-carboxylic acids is selected from acetic acid,    acetylsalicylic acid, adipic acid, alginic acid, arachidic acid,    ascorbic acid, aspartic acid, benzenesulfonic acid, benzoic acid,    bisulfic acid, boric acid, butyric acid, camphoric acid,    camphorsulfonic acid, capric acid, caproic acid, caprylic acid,    carbonic acid, citric acid, cyclopentanepropionic acid, digluconic    acid, dodecylsulfic acid, enanthic acid, ethanesulfonic acid, formic    acid, fumaric acid, glucoheptanoic acid, gluconic acid, glutamic    acid, glutaric acid, glyceric acid, glycerophosphoric acid, glycine,    glycolic acid, hemisulfic acid, heptanoic acid, hexanoic acid,    hippuric acid, hydrobromic acid, hydrochloric acid, hydroiodic acid,    hydroxyethanesulfonic acid, lactic acid, lauric acid, maleic acid,    malic acid, malonic acid, mandelic acid, margaric acid,    methanesulfonic acid, mucic acid, myristic acid, naphthylanesulfonic    acid, naphthylic acid, nicotinic acid, nonadecylic acid, oxalic    acid, oxalic acid, palmitic acid, pelargonic, pelargonic acid,    pentadecylic acid, phosphoric acid, propionic acid, saccharin,    salicylic acid, sorbic acid, stearic acid, succinic acid, sulfuric    acid, tartaric acid, thiocyanic acid, thioglycolic acid,    thiosulfuric acid, tosylic acid, trichloroacetic acid, tridecylic    acid, trifluoroacetic acid, undecylenic acid, undecylic acid,    valeric acid;-   triose sugars are selected from D- or L-glyceraldehyde;-   tetrose sugars are selected from D- or L-erythrose or threose, and    their deoxy counterparts;-   pentose sugars are selected from D- or L-arabinose, lyxose, ribose,    xylose, ribulose, or xylulose, and their deoxy counterparts;-   hexose sugars are selected from D- or L-allose, altrose, glucose,    mannose, gulose, idose, galactose, talose, psicose, fructose,    sorbose, tagatose, and their deoxy counterparts;-   and amino acids are selected from alanine, arginine, asparagine,    aspartic acid, cysteine, glutamine, glutamic acid, glycine,    histidine, isoleucine, leucine, lysine, methionine, phenylalanine,    proline, serine, threonine, tryptophan, tyrosine, valine, omithine,    citrulline, taurine, selenocysteine, pyrrolysine, aminobutyic acid,    gama-aminobutryic acid, 3-aminopropanoic acid, dehydroalanine,    delta-carboxyglutamic acid, N-formylmethionine.

In another embodiment, the tryptamine comprises a compound having thestructure of Formula 2A or 2B,

-   wherein:-   R₁ is H, OH, COOH, OCH₃, O(CH₂)_(n)CH₃, (CH₂)_(n)OH, (CH₂)_(n)COOH,    —C(O)CH₃, (CH₂)_(n)OC(O)N(R₆)₂, —(CH₂)_(n)C(O)OC(O)OH, PO₄, P₂O₇,    P₃O₁₀, SO₄, S₂O₇, S₃O₁₀, CHO₃, a C₁-C₈ mono-di-, or tri-carboxylic    acid, a triose sugar, a tetrose sugar, a pentose sugar, a hexose    sugar, or an amino acid;-   R₂ and R₃ are independently H, CH₃, C₁-C₄ alkyl, C₁-C₄ allyl, C₁-C₄    ethynyl, OH, COOH, (CH₂)_(n)COOH; OCH₃, O(CH₂)_(n)CH₃, (CH₂)_(n)OH,    (CH₂)_(n)NH₂; dimethyl amine, pyrrole, pyrazole, imidazole,    pyridine, piperdine, pyridine, pyrimidine, indole, purine,    quinoline, morpholino, pyran, or furan;-   R₄ is H, CH₃, OH, CHOCH₃, (CH₂)_(n)OH, OCH₃, O(CH₂)_(n)CH₃;-   R₅ is H, CH₃, OH, CHOCH₃, (CH₂)_(n)OH, OCH₃, O(CH₂)_(n)CH₃ or    (CH₂)_(n)CH₃; and-   R₆ is H, CH₃, C₁-C₄ alkyl, OH, CHOCH₃, (CH₂)_(n)OH, OCH₃,    O(CH₂)_(n)CH₃;-   where n is 0, 1, 2, 3, or 4;-   wherein-   mono-, di-, and tri-carboxylic acids is selected from acetic acid,    acetylsalicylic acid, adipic acid, alginic acid, arachidic acid,    ascorbic acid, aspartic acid, benzenesulfonic acid, benzoic acid,    bisulfic acid, boric acid, butyric acid, camphoric acid,    camphorsulfonic acid, capric acid, caproic acid, caprylic acid,    carbonic acid, citric acid, cyclopentanepropionic acid, digluconic    acid, dodecylsulfic acid, enanthic acid, ethanesulfonic acid, formic    acid, fumaric acid, glucoheptanoic acid, gluconic acid, glutamic    acid, glutaric acid, glyceric acid, glycerophosphoric acid, glycine,    glycolic acid, hemisulfic acid, heptanoic acid, hexanoic acid,    hippuric acid, hydrobromic acid, hydrochloric acid, hydroiodic acid,    hydroxyethanesulfonic acid, lactic acid, lauric acid, maleic acid,    malic acid, malonic acid, mandelic acid, margaric acid,    methanesulfonic acid, mucic acid, myristic acid, naphthylanesulfonic    acid, naphthylic acid, nicotinic acid, nonadecylic acid, oxalic    acid, oxalic acid, palmitic acid, pelargonic, pelargonic acid,    pentadecylic acid, phosphoric acid, propionic acid, saccharin,    salicylic acid, sorbic acid, stearic acid, succinic acid, sulfuric    acid, tartaric acid, thiocyanic acid, thioglycolic acid,    thiosulfuric acid, tosylic acid, trichloroacetic acid, tridecylic    acid, trifluoroacetic acid, undecylenic acid, undecylic acid,    valeric acid;-   triose sugars are selected from D- or L-glyceraldehyde;-   tetrose sugars are selected from D- or L-erythrose or threose, and    their deoxy counterparts;-   pentose sugars are selected from D- or L-arabinose, lyxose, ribose,    xylose, ribulose, or xylulose, and their deoxy counterparts;-   hexose sugars are selected from D- or L-allose, altrose, glucose,    mannose, gulose, idose, galactose, talose, psicose, fructose,    sorbose, tagatose, and their deoxy counterparts;-   and amino acids are selected from alanine, arginine, asparagine,    aspartic acid, cysteine, glutamine, glutamic acid, glycine,    histidine, isoleucine, leucine, lysine, methionine, phenylalanine,    proline, serine, threonine, tryptophan, tyrosine, valine, omithine,    citrulline, taurine, selenocysteine, pyrrolysine, aminobutyric acid,    gama-aminobutryic acid, 3-aminopropanoic acid, dehydroalanine,    delta-carboxyglutamic acid, N-formylmethionine.

In another embodiment, the tryptamine comprises a compound having thestructure of Formula 3A or 3B,

-   wherein:-   R₁ is H, OH, COOH, OCH₃, O(CH₂)_(n)CH₃, (CH₂)_(n)OH, (CH₂)_(n)COOH,    C(O)CH₃, (CH₂)_(n)OC(O)N(R₆)₂, (CH₂)_(n)C(O)OC(O)OH, PO₄, P₂O₇,    P₃O₁₀, SO₄, S₂O₇, S₃O₁₀, CHO₃, a C₁-C₂₂ mono-di-, or tri-carboxylic    acid, a pentose sugar, a hexose sugar, or an amino acid;-   R₂ and R₃ are independently H, CH₃, (CH₂)_(n)CH₃, OH, COOH,    (CH₂)_(n)COOH; OCH₃, O(CH₂)_(n)CH₃, (CH₂)_(n)OH, (CH₂)_(n)NH₂;    dimethyl amine, pyrrole, pyrazole, imidazole, pyridine, piperdine,    pyridine, pyrimidine, indole, purine, quinoline, morpholino, pyran,    or furan;-   R₄ is H, CH₃, OH, CHOCH₃, (CH₂)_(n)OH, OCH₃, O(CH₂)_(n)CH₃;-   R₅ is H, CH₃, C₁-C₄ alkyl, OH, CHOCH₃, (CH₂)_(n)OH, OCH₃,    O(CH₂)_(n)CH₃ or (CH₂)_(n)CH₃; and-   R₆ is H, CH₃, C₁-C₄ alkyl, OH, CHOCH₃, (CH₂)_(n)OH, OCH₃,    O(CH₂)_(n)CH₃;-   where n is 0, 1, 2, 3, or 4; and-   wherein-   mono-, di-, and tri-carboxylic acids is selected from acetic acid,    acetylsalicylic acid, adipic acid, alginic acid, arachidic acid,    ascorbic acid, aspartic acid, benzenesulfonic acid, benzoic acid,    bisulfic acid, boric acid, butyric acid, camphoric acid,    camphorsulfonic acid, capric acid, caproic acid, caprylic acid,    carbonic acid, citric acid, cyclopentanepropionic acid, digluconic    acid, dodecylsulfic acid, enanthic acid, ethanesulfonic acid, formic    acid, fumaric acid, glucoheptanoic acid, gluconic acid, glutamic    acid, glutaric acid, glyceric acid, glycerophosphoric acid, glycine,    glycolic acid, hemisulfic acid, heptanoic acid, hexanoic acid,    hippuric acid, hydrobromic acid, hydrochloric acid, hydroiodic acid,    hydroxyethanesulfonic acid, lactic acid, lauric acid, maleic acid,    malic acid, malonic acid, mandelic acid, margaric acid,    methanesulfonic acid, mucic acid, myristic acid, naphthylanesulfonic    acid, naphthylic acid, nicotinic acid, nonadecylic acid, oxalic    acid, oxalic acid, palmitic acid, pelargonic, pelargonic acid,    pentadecylic acid, phosphoric acid, propionic acid, saccharin,    salicylic acid, sorbic acid, stearic acid, succinic acid, sulfuric    acid, tartaric acid, thiocyanic acid, thioglycolic acid,    thiosulfuric acid, tosylic acid, trichloroacetic acid, tridecylic    acid, trifluoroacetic acid, undecylenic acid, undecylic acid,    valeric acid;-   triose sugars are selected from D- or L-glyceraldehyde;-   tetrose sugars are selected from D- or L-erythrose or threose, and    their deoxy counterparts;-   pentose sugars are selected from D- or L-arabinose, lyxose, ribose,    xylose, ribulose, or xylulose, and their deoxy counterparts;-   hexose sugars are selected from D- or L-allose, altrose, glucose,    mannose, gulose, idose, galactose, talose, psicose, fructose,    sorbose, tagatose, and their deoxy counterparts;-   and amino acids are selected from alanine, arginine, asparagine,    aspartic acid, cysteine, glutamine, glutamic acid, glycine,    histidine, isoleucine, leucine, lysine, methionine, phenylalanine,    proline, serine, threonine, tryptophan, tyrosine, valine, omithine,    citrulline, taurine, selenocysteine, pyrrolysine, aminobutyic acid,    gama-aminobutryic acid, 3-aminopropanoic acid, dehydroalanine,    delta-carboxyglutamic acid, N-formylmethionine.

In one embodiment, the tryptamine comprises a compound having thestructure of Formula 4A or 4B,

-   wherein:-   R₁ is H, OH, COOH, OCH₃, O(CH₂)_(n)CH₃, (CH₂)_(n)OH, (CH₂)_(n)COOH,    —C(O)CH₃, (CH₂)_(n)OC(O)N(R₆)₂, —(CH₂)_(n)C(O)OC(O)OH, PO₄, P₂O₇,    P₃O₁₀, SO₄, S₂O₇, S₃O₁₀, CHO₃, a C₁-C₆ mono-di-, or tri-carboxylic    acid, a pentose sugar, a hexose sugar, or an amino acid;-   R₂ and R₃ are independently H, CH₃, OH, COOH, (CH₂)_(n)COOH; OCH₃,    O(CH₂)_(n)CH₃, (CH₂)_(n)OH, (CH₂)_(n)NH₂; dimethyl amine, pyrrole,    pyrazole, imidazole, pyridine, piperdine, pyridine, pyrimidine,    indole, purine, quinoline, morpholino, pyran, or furan;-   R₄ is H, CH₃, OH, (CH₂)_(n)OH, OCH₃, O(CH₂)_(n)CH₃; and-   R₆ is H, CH₃, C₁-C₄ alkyl, OH, CHOCH₃, (CH₂)_(n)OH, OCH₃,    O(CH₂)_(n)CH₃;-   where n is 0, 1, 2, 3, or 4; and-   wherein-   mono-, di-, and tri-carboxylic acids is selected from acetic acid,    acetylsalicylic acid, adipic acid, alginic acid, arachidic acid,    ascorbic acid, aspartic acid, benzenesulfonic acid, benzoic acid,    bisulfic acid, boric acid, butyric acid, camphoric acid,    camphorsulfonic acid, capric acid, caproic acid, caprylic acid,    carbonic acid, citric acid, cyclopentanepropionic acid, digluconic    acid, dodecylsulfic acid, enanthic acid, ethanesulfonic acid, formic    acid, fumaric acid, glucoheptanoic acid, gluconic acid, glutamic    acid, glutaric acid, glyceric acid, glycerophosphoric acid, glycine,    glycolic acid, hemisulfic acid, heptanoic acid, hexanoic acid,    hippuric acid, hydrobromic acid, hydrochloric acid, hydroiodic acid,    hydroxyethanesulfonic acid, lactic acid, lauric acid, maleic acid,    malic acid, malonic acid, mandelic acid, margaric acid,    methanesulfonic acid, mucic acid, myristic acid, naphthylanesulfonic    acid, naphthylic acid, nicotinic acid, nonadecylic acid, oxalic    acid, oxalic acid, palmitic acid, pelargonic, pelargonic acid,    pentadecylic acid, phosphoric acid, propionic acid, saccharin,    salicylic acid, sorbic acid, stearic acid, succinic acid, sulfuric    acid, tartaric acid, thiocyanic acid, thioglycolic acid,    thiosulfuric acid, tosylic acid, trichloroacetic acid, tridecylic    acid, trifluoroacetic acid, undecylenic acid, undecylic acid,    valeric acid;-   triose sugars are selected from D- or L-glyceraldehyde;-   tetrose sugars are selected from D- or L-erythrose or threose, and    their deoxy counterparts;-   pentose sugars are selected from D- or L-arabinose, lyxose, ribose,    xylose, ribulose, or xylulose, and their deoxy counterparts;-   hexose sugars are selected from D- or L-allose, altrose, glucose,    mannose, gulose, idose, galactose, talose, psicose, fructose,    sorbose, tagatose, and their deoxy counterparts;-   and amino acids are selected from alanine, arginine, asparagine,    aspartic acid, cysteine, glutamine, glutamic acid, glycine,    histidine, isoleucine, leucine, lysine, methionine, phenylalanine,    proline, serine, threonine, tryptophan, tyrosine, valine, omithine,    citrulline, taurine, selenocysteine, pyrrolysine, aminobutync acid,    gama-aminobutryic acid, 3-aminopropanoic acid, dehydroalanine,    delta-carboxyglutamic acid, N-formylmethionine.

In another embodiment, the tryptamine comprises a compound having thestructure of Formula 5A or 5B:

wherein each R is independently H, CH₃, CH₃CH₂, CH₃CH₂CH₂, (CH₃)₂CH,CH₂CH═CH, OCH₃, OC₁-C₄ alkyl, CH₂OH, C₁-C₃ alkyl-OH, COOH, C₁-C₃alkyl-COOH, or a pharmaceutically acceptable salt, hydrate, solvate, ortautomer thereof, or a combination thereof.

In another embodiment the tryptamine comprises a compound having thestructure of:

In another embodiment, the erinacine comprises Erinacine A, Erinacine B,Erinacine C, Erinacine D, Erinacine E, Erinacine F, Erinacine G,Erinacine H, Erinacine I, Erinacine J, Erinacine K, Erinacine P,Erinacine Q, Erinacine R, Erinacol, other Erinacines or apharmaceutically acceptable salt, hydrate, solvate, prodrug,stereoisomer, or tautomer thereof, or a combination thereof.

In another embodiment, the erinacine comprises a compound having thestructure of:

In another embodiment, the hericenone comprises Hericenone A, HericenoneB, Hericenone C, Hericenone D, Hericenone E, Hericenone F, Hericenone G,Hericenone H, other hericenones, or a pharmaceutically acceptable salt,hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, or acombination thereof.

In another embodiment, the hericenone comprises a compound having thestructure of:

In another embodiment, the active compound is a compound isolated andidentified in an extract from Hericium erinaceus.

In another embodiment, the cannabinoid comprises Δ8-tetrahydrocannabinol(THC), Δ9-tetrahydrocannabinol, tetrahydrocannabinolic acid (THCA),cannabidiol (CBD), cannabidiolic acid (CBDA), cannabinol (CBN),cannabigerol (CBG), cannabichromene (CBC), cannabicyclol (CBL),cannabivarin (CBV), tetrahydrocannabivarin (THCV), cannabidivarin(CBDV), cannabichromevarin (CBCV), cannabigerovarin (CBGV), cannabigerolmonomethyl ether (CBGM), cannabielsoin (CBE), cannabicitran (CBT), othercannabinoids, or a pharmaceutically acceptable salt, hydrate, solvate,prodrug, stereoisomer, or tautomer thereof, or a combination thereof.

In another embodiment, the cannabinoid comprises a compound having thestructure of:

In another embodiment, the compositions described herein comprises oneor more natural products such as aliphatic natural products, alkaloids,amino acids, anthranilic acid alkaloids, apiole, (+)-aromadendrene,asarone, aurones, benzofuranoids, benzofurans, benzophenones,benzopyranoids, benzopyrans, benztropolones, cis-α-bergamotene,trans-α-bergamotene, α-bisabolol, bomeol, γ-cadinene, caffeic acid,camphor, carbohydrates, carotenoids, 3-carene, β-carbolines,trans-β-caryophyllene, catechins, chalcones, chavicol, chavicols,chromones, cineol, cinnamic acid, cinnamic aldehydes, cinnamicmonolignols, conferyl alcohol, coniferyl alcohol, cordysinin, coumarins,coumaric acid, coumaryl alcohol, cutin, depsides, depsidones,dillapiole, diterpenes, diterpenoids, γ-elemene, elemicin,eleutherosides, esterterpenoids, estragole, eudesman-3,7(11)-diene,β-eudesmol, γ-eudesmol, eugenol, trans-β-farnesene, ferulic acid,haramane, harmine, norharmine, harmol, α-humuline, β-fenchol,5-hydroxyferulic acid, flavonoids, glycopeptides, hydroxycinnamic acids,hydroxylated fatty acids, imidazole alkaloids, isoflavonoids,isoquinoline alkaloids, β-lactams, lignans, limonoids, R-limonene,(−)-linalool, lipids, lysine alkaloids, meroterpenoids, methyl eugenol,miscellaneous terpenoids, monoterpenoid indole alkaloids,monoterpenoids, myrcene, myristicin, nerolidol, nicotinic acidalkaloids, cis-ocimene, 1-octanol, omithine alkaloids, otenoids, oxazolealkaloids, oxygen heterocycles, peptides, phellanderene, phenolics,phenylalanine alkaloids, phenylpropanoids, phenylpropanoids,phenylpropenes, perlolyrine, pinene, polycyclic aromatic naturalproducts, polyketide alkaloids, polyketides, polypyrroles, ptteridines,purines, putrescine alkaloids, pyrazine alkaloids, pyrimidines, pyrrolealkaloids, quassinoids, quinonemethides, quinones, quinoxalinealkaloids, resveratrol, trans-resveratrol, cis-sabinene hydrate,safrole, γ-selinene, semiochemicals, septide alkaloids, sesquiterpenes,sesquiterpenoids, simple aromatic natural products, sinapic acid,sinapyl alcohols, spermidine alkaloids, spermine alkaloids,sporopollenin, steroidal alkaloids, steroids, sterols, stilbenes,stilbenoids, suberin, tannins, terpenoid alkaloids, terpenoids,γ-terpinene, α-terpineol, terpinolene, tetraterpenoids, thiazolealkaloids, triterpenes, triterpenoids, tryptophan alkaloids, tyrosinealkaloids, umbelliferone, xanthones, or a pharmaceutically acceptablesalt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, or acombination thereof.

In another embodiment, the compositions described herein comprises aphenethylamine or an amphetamine compound selected from:α-ethyl-3,4,5-trimethoxy-phenethylamine (AEM),4-allyloxy-3,5-dimethoxy-phenethylamine (AL),4-methylthio-2,5-dimethoxy-amphetamine (ALEPH),4-ethylthio-2,5-dimethoxy-amphetamine (ALEPH-2),4-isopropylthio-2,5-dimethoxy-amphetamine (ALEPH-4),4-phenylthio-2,5-dimethoxy-amphetamine (ALEPH-6),4-propylthio-2,5-dimethoxy-amphetamine (ALEPH-7),2,5-dimethoxy-α-ethyl-4-methyl-phenethylamine (ARIADNE),3,4-diethoxy-5-methoxy-phenethylamine (ASB),4-butoxy-3,5-dimethoxy-phenethylamine (B),2,5-dimethoxy-4,N-dimethyl-amphetamine (BEATRICE),2,5-bismethylthio-4-methyl-amphetamine (BIS-TOM),4-bromo-2,5,β-trimethoxy-phenethylamine (BOB),2,5,β-trimethoxy-4-methyl-phenethylamine (BOD),β-methoxy-3,4-methylenedioxy-phenethylamine (BOH),2,5-dimethoxy-β-hydroxy-4-methyl-phenethylamine (BOHD),3,4,5,β-tetramethoxy-phenethylamine (BOM),4-bromo-3,5-dimethoxy-amphetamine (4-Br-3,5-DMA),2-bromo-4,5-methylenedioxy-amphetamine (2-Br-4,5-MDA),4-bromo-2,5-dimethoxy-phenethylamine (2C-B),4-benzyloxy-3,5-dimethoxy-amphetamine (3C-BZ),4-chloro-2,5-dimethoxy-phenethylamine (2C-C),4-methyl-2,5-dimethoxy-phenethylamine (2C-D),4-ethyl-2,5-dimethoxy-phenethylamine (2C-E),4-ethoxy-3,5-dimethoxy-amphetamine (3C-E),4-fluoro-2,5-dimethoxy-phenethylamine (2C-F),3,4-dimethyl-2,5-dimethoxy-phenethylamine (2C-G),3,4-trimethylene-2,5-dimethoxy-phenethylamine (2C-G-3),3,4-tetramethylene-2,5-dimethoxy-phenethylamine (2C-G-4),3,4-norbornyl-2,5-dimethoxy-phenethylamine (2C-G-5),1,4-dimethoxynaphthyl-2-ethylamine (2C-G-N),2,5-dimethoxy-phenethylamine (2C-H), 4-iodo-2,5-dimethoxy-phenethylamine(2C-1), 4-nitro-2,5-dimethoxy-phenethylamine (2C-N),4-isopropoxy-2,5-dimethoxy-phenethylamine (2C-O-4),4-propyl-2,5-dimethoxy-phenethylamine (2C-P),4-cyclopropylmethoxy-3,5-dimethoxy-phenethylamine (CPM),4-methylseleno-2,5-dimethoxy-phenethylamine (2C-SE),4-methylthio-2,5-dimethoxy-phenethylamine (2C-T),4-ethylthio-2,5-dimethoxy-phenethylamine (2C-T-2),4-isopropylthio-2,5-dimethoxy-phenethylamine (2C-T-4),4-isopropylthio-2,6-dimethoxy-phenethylamine (psi-2C-T-4),4-propylthio-2,5-dimethoxy-phenethylamine (2C-T-7),4-cyclopropylmethylthio-2,5-dimethoxy-phenethylamine (2C-T-8),4-(t)-butylthio-2,5-dimethoxy-phenethylamine (2C-T-9),4-(2-methoxyethylthio)-2,5-dimethoxy-phenethylamine (2C-T-13),4-cyclopropylthio-2,5-dimethoxy-phenethylamine (2C-T-15),4-(s)-butylthio-2,5-dimethoxy-phenethylamine (2C-T-17),4-(2-fluoroethylthio)-2,5-dimethoxy-phenethylamine (2C-T-21),4-trideuteromethyl-3,5-dimethoxy-phenethylamine (4-D),β,β-dideutero-3,4,5-trimethoxy-phenethylamine (β-D),4-methyl-3,5-dimethoxy-phenethylamine (DESOXY),2,4-dimethoxy-amphetamine (2,4-DMA), 2,5-dimethoxy-amphetamine(2,5-DMA), 3,4-dimethoxy-amphetamine (3,4-DMA),2-(2,5-dimethoxy-4-methylphenyl)-cyclopropylamine (DMCPA),3,4-dimethoxy-β-hydroxy-phenethylamine (DME),2,5-dimethoxy-3,4-methylenedioxy-amphetamine (DMMDA),2,3-dimethoxy-4,5-methylenedioxy-amphetamine (DMMDA-2),3,4-dimethoxy-phenethylamine (DMPEA), 4-amyl-2,5-dimethoxy-amphetamine(DOAM), 4-bromo-2,5-dimethoxy-amphetamine (DOB),4-butyl-2,5-dimethoxy-amphetamine (DOBU),4-chloro-2,5-dimethoxy-amphetamine (DOC),4-(2-fluoroethyl)-2,5-dimethoxy-amphetamine (DOEF),4-ethyl-2,5-dimethoxy-amphetamine (DOET),4-iodo-2,5-dimethoxy-amphetamine (DOI),4-methyl-2,5-dimethoxy-amphetamine (DOM (STP)),4-methyl-2,6-dimethoxy-amphetamine (psi-DOM),4-nitro-2,5-dimethoxy-amphetamine (DON),4-propyl-2,5-dimethoxy-amphetamine (DOPR),4-ethoxy-3,5-dimethoxy-phenethylamine (E), 2,4,5-triethoxy-amphetamine(EEE), 2,4-diethoxy-5-methoxy-amphetamine (EEM),2,5-diethoxy-4-methoxy-amphetamine (EME),2-ethoxy-4,5-dimethoxy-amphetamine (EMM),N,α-diethyl-3,4-methylenedioxy-phenethylamine (ETHYL-J),N-ethyl-α-propyl-3,4-methylenedioxy-phenethylamine (ETHYL-K),benzofuran-2-methyl-5-methoxy-6-(2-aminopropane) (F-2),benzofuran-2,2-dimethyl-5-methoxy-6-(2-aminopropane) (F-22),N-hydroxy-N-methyl-3,4-methylenedioxy-amphetamine (FLEA),3,4-trimethylene-2,5-dimethoxy-amphetamine (G-3),3,4-tetramethylene-2,5-dimethoxy-amphetamine (G-4),3,4-norbornyl-2,5-dimethoxy-amphetamine (G-5),3,4-dimethyl-2,5-dimethoxy-amphetamine (GANESHA),1,4-dimethoxynaphthyl-2-isopropylamine (G-N),2,5-dimethoxy-N-hydroxy-4-ethylthio-phenethylamine (HOT-2),2,5-dimethoxy-N-hydroxy-4-(n)-propylthio-phenethylamine (HOT-7),2,5-dimethoxy-N-hydroxy-4-(s)-butylthio-phenethylamine (HOT-17),2,5-dimethoxy-N,N-dimethyl-4-iodo-amphetamine (IDNNA),2,3,4-trimethoxy-phenethylamine (IM),3,5-dimethoxy-4-isopropoxy-phenethylamine (IP),5-ethoxy-2-methoxy-4-methyl-amphetamine (IRIS),α-ethyl-3,4-methylenedioxy-phenethylamine (J),3-methoxy-4,5-methylenedioxy-phenethylamine (LOPHOPHINE),3,4,5-trimethoxy-phenethylamine (M), 4-methoxy-amphetamine (4-MA),2,N-dimethyl-4,5-methylenedioxy-amphetamine (MADAM-6),3,5-dimethoxy-4-methallyloxy-phenethylamine (MAL),3,4-methylenedioxy-amphetamine (MDA),N-allyl-3,4-methylenedioxy-amphetamine (MDAL),N-butyl-3,4-methylenedioxy-amphetamine (MDBU),N-benzyl-3,4-methylenedioxy-amphetamine (MDBZ),N-Cyclopropylmethyl-3,4-methylenedioxy-amphetamine (MDCPM),N,N-dimethyl-3,4-methylenedioxy-amphetamine (MDDM),N-ethyl-3,4-methylenedioxy-amphetamine (MDE),N-(2-hydroxyethyl)-3,4-methylenedioxy-amphetamine (MDHOET),N-isopropyl-3,4-methylenedioxy-amphetamine (MDIP),N-methyl-3,4-methylenedioxy-amphetamine (MDMA),N-methyl-3,4-ethylenedioxy-amphetamine (MDMC),N-methoxy-3,4-methylenedioxy-amphetamine (MDMEO),N-(2-methoxyethyl)-3,4-methylenedioxy-amphetamine (MDMEOET),α,α,N-trimethyl-3,4-methylenedioxy-phenethylamine (MDMP),N-hydroxy-3,4-methylenedioxy-amphetamine (MDOH),3,4-methylenedioxy-phenethylamine (MDPEA),α,α-dimethyl-3,4-methylenedioxy-phenethylamine (MDPH),N-propargyl-3,4-methylenedioxy-amphetamine (MDPL),N-propyl-3,4-methylenedioxy-amphetamine (MDPR),3,4-dimethoxy-5-ethoxy-phenethylamine (ME),3-methoxy-4,5-ethylenedioxy-amphetamine (MEDA),2-methoxy-4,5-diethoxy-amphetamine (MEE),2,5-dimethoxy-4-ethoxy-amphetamine (MEM),3-methoxy-4-ethoxy-phenethylamine (MEPEA),5-bromo-2,4-dimethoxy-amphetamine (META-DOB),5-methylthio-2,4-dimethoxy-amphetamine (META-DOT),N-methyl-2,5-dimethoxy-amphetamine (METHYL-DMA),4-bromo-2,5-dimethoxy-N-methyl-amphetamine (METHYL-DOB),N-methyl-α-ethyl-3,4-methylenedioxy-phenethylamine (METHYL-J),N-methyl-α-propyl-3,4-methylenedioxy-phenethylamine (METHYL-K),N-methyl-4-methoxy-amphetamine (METHYL-MA),N-methyl-2-methoxy-4,5-methylenedioxy-amphetamine (METHYL-MMDA-2),3-methoxy-4,5-methylenedioxy-amphetamine (MMDA),2-methoxy-4,5-methylenedioxy-amphetamine (MMDA-2),2-methoxy-3,4-methylenedioxy-amphetamine (MMDA-3a),4-methoxy-2,3-methylenedioxy-amphetamine (MMDA-3b),2,4-dimethoxy-5-ethoxy-amphetamine (MME),3,4-dimethoxy-5-propoxy-phenethylamine (MP),2,5-dimethoxy-4-propoxy-amphetamine (MPM),2-methylthio-4,5-dimethoxy-amphetamine (ORTHO-DOT),3,5-dimethoxy-4-propoxy-phenethylamine (P),3,5-dimethoxy-4-phenethyloxy-phenethylamine (PE), phenethylamine (PEA),4-propynyloxy-3,5-dimethoxy-phenethylamine (PROPYNYL),3,5-diethoxy-4-methoxy-phenethylamine (SB),2,3,4,5-Tetramethoxy-amphetamine (TA),4-ethoxy-3-ethylthio-5-methoxy-phenethylamine (3-TASB),3-ethoxy-4-ethylthio-5-methoxy-phenethylamine (4-TASB),3,4-diethoxy-5-methylthio-phenethylamine (5-TASB),4-thiobutoxy-3,5-dimethoxy-phenethylamine (TB),4-ethoxy-5-methoxy-3-methylthio-phenethylamine (3-TE),3,5-dimethoxy-4-ethylthio-phenethylamine (4-TE),2-methylthio-3,4-dimethoxy-phenethylamine (2-TIM),3-methylthio-2,4-dimethoxy-phenethylamine (3-TIM),4-methylthio-2,3-dimethoxy-phenethylamine (4-TIM),3-methylthio-4,5-dimethoxy-phenethylamine (3-TM),4-methylthio-3,5-dimethoxy-phenethylamine (4-TM),3,4,5-trimethoxy-amphetamine (TMA), 2,4,5-trimethoxy-amphetamine(TMA-2), 2,3,4-trimethoxy-amphetamine (TMA-3),2,3,5-trimethoxy-amphetamine (TMA-4), 2,3,6-trimethoxy-amphetamine(TMA-5), 2,4,6-trimethoxy-amphetamine (TMA-6),4,5-dimethoxy-3-ethylthio-phenethylamine (3-TME),3-ethoxy-5-methoxy-4-methylthio-phenethylamine (4-TME),3-ethoxy-4-methoxy-5-methylthio-phenethylamine (5-TME),2-methylthio-3,4-methylenedioxy-amphetamine (2T-MMDA-3a),4,5-thiomethyleneoxy-2-methoxy-amphetamine (4T-MMDA-2),2,4,5-trimethoxy-phenethylamine (TMPEA),4-ethyl-5-methoxy-2-methylthio-amphetamine (2-TOET),4-ethyl-2-methoxy-5-methylthio-amphetamine (5-TOET),5-methoxy-4-methyl-2-methylthio-amphetamine (2-TOM),2-methoxy-4-methyl-5-methylthio-amphetamine (5-TOM),2-methoxy-4-methyl-5-methylsulfinyl-amphetamine (TOMSO),4-propylthio-3,5-dimethoxy-phenethylamine (TP),3,4,5-triethoxy-phenethylamine (TRIS),3-ethoxy-5-ethylthio-4-methoxy-phenethylamine (3-TSB),3,5-diethoxy-4-methylthio-phenethylamine (4-TSB),4,5-diethoxy-3-ethylthio-phenethylamine (3-T-TRIS),3,5-diethoxy-4-ethylthio-phenethylamine (4-T-TRIS),(R)-2,5-dimethoxy-4-iodoamphetamine, or a pharmaceutically acceptablesalt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, or acombination thereof. See Shulgin and Shulgin, PIHKAL: A Chemical LoveStory, Transform Press (1994), which is incorporated by reference hereinfor the specific teachings thereof. In some embodiments, the amphetaminemay be (R)-2,5-dimethoxy-4-iodoamphetamine or a pharmaceuticallyacceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomerthereof. (R)-2,5-dimethoxy-4-iodoamphetamine (i.e., 2C-H) isstructurally similar to the popular psychedelic drug 2C-B (which issimilar to ecstasy and MDMA), but it does not itself have anypsychoactive effects. It was found to activate the 5-HT_(2A) receptorand prevent and reverse inflammation in the lungs. Flanagan and Nichols,Int. Review of Psychiatry, 30(4): 363-375 (2018). In another embodiment,the amphetamine comprises (R)-2,5-dimethoxy-4-iodoamphetamine, havingthe structure:

It will be apparent to one of ordinary skill in the relevant art thatsuitable modifications and adaptations to the compositions,formulations, methods, processes, and applications described herein canbe made without departing from the scope of any embodiments or aspectsthereof. The compositions and methods provided are exemplary and are notintended to limit the scope of any of the specified embodiments. All thevarious embodiments, aspects, and options disclosed herein can becombined in any variations or iterations. The scope of the compositions,formulations, methods, and processes described herein include all actualor potential combinations of embodiments, aspects, options, examples,preferences, or steps described herein. The exemplary compositions,formulations, and methods described herein may omit any component orstep described herein, substitute any component or step describedherein, or include any component or step described elsewhere herein. Theratios of the mass of any component of any of the compositions orformulations disclosed herein to the mass of any other component in theformulation or to the total mass of the other components in theformulation are hereby disclosed as if they were expressly disclosed.Should the meaning of any terms in any of the patents or publicationsincorporated by reference conflict with the meaning of the terms used inthis disclosure, the meanings of the terms or phrases in this disclosureare controlling.

Furthermore, the foregoing description discloses exemplary embodiments.All patents and publications cited herein are incorporated by referenceherein for the specific teachings thereof.

EXAMPLES Example 1

Hericium erinaceus Extracts Extracts were prepared from Hericiumerinaceus mycelium or fruiting bodies colonized on rice or rice and oathull fiber for various time periods.

H. erinaceus was cultivated, frozen and ground and extracted in waterfor 2 h at room temperature. The extract was filtered through Whatmanfilter via gravity. The filtrate was lyophilized to dryness.

Ethanol extracts were made from the same H. erinaceus mycelium. Themycelium was frozen, but not ground, and extracted in 70% ethanol for 1week at room temperature. The extract was filtered through an 80-meshsieve and lyophilized to dryness.

A portion of the ethanol extract was rotovapped to dryness and theresidue resuspended in 1:1 water:ethyl acetate. The water/ethyl acetateextract was washed 3 times with ethyl acetate, the combined organicfractions dried over MgSO₄, filtered, rotovapped, and then lyophilized.

Example 2

Experiments were conducted to evaluate the neurotrophic effects ofseveral purified tryptamines, H. erinaceum extracts, and the tryptaminescombined with selected extracts of H. erinaceum. The tryptamines,baeocystin, norbaeocystin, and norpsilocin, were evaluated at finalconcentrations of 0.3 μg/mL, 1 μg/mL, 3 μg/mL, and 10 μg/mL. Theexperiments analyzed the H. erinaceum growth medium (rice or rice andoat hull fiber), the days of cultivation, the extract solvent (water,ethanol, or ethyl acetate), and the final concentration of the extract(31.3 μg/mL, 62.5 μg/mL, 125 μg/mL or 250 μg/mL). Finally, combinationsof the three tryptamines and representative H. erinaceum extracts werecombined and evaluated.

The test compositions are shown in Table 4.

TABLE 4 Test Compositions He mycelium, rice 12 d, H₂O 31.3 μg/mL Hemycelium, rice 12 d, H₂O 62.5 μg/mL He mycelium, rice 12 d, H₂O 125μg/mL He mycelium, rice 12 d, H₂O 250 μg/mL He mycelium, rice 12 d, EtOH31.3 μg/mL He mycelium, rice 12 d, EtOH 62.5 μg/mL He mycelium, rice 12d, EtOH 125 μg/mL He mycelium, rice 12 d, EtOH 250 μg/mL He mycelium,rice 12 d, EtOAc 31.3 μg/mL He mycelium, rice 12 d, EtOAc 62.5 μg/mL Hemycelium, rice 12 d, EtOAc 125 μg/mL He mycelium, rice 12 d, EtOAc 250μg/mL He mycelium, rice, oat hut 21 d, H₂O 31.3 μg/mL He mycelium, rice,oat hut 21 d, H₂O 62.5 μg/mL He mycelium, rice, oat hut 21 d, H₂O 125μg/mL He mycelium, rice, oat hut 21 d, H₂O 250 μg/mL He mycelium, rice,oat hut 21 d, EtOH 31.3 μg/mL He mycelium, rice, oat hut 21 d, EtOH 62.5μg/mL He mycelium, rice, oat hut 21 d, EtOH 125 μg/mL He mycelium, rice,oat hut 21 d, EtOH 250 μg/mL He mycelium, rice, oat hut 21 d, EtOAc 31.3μg/mL He mycelium, rice, oat hut 21 d, EtOAc 62.5 μg/mL He mycelium,rice, oat hut 21 d, EtOAc 125 μg/mL He mycelium, rice, oat hut 21 d,EtOAc 250 μg/mL He mycelium, rice, oat hut 98 d, H₂O 31.3 μg/mL Hemycelium, rice, oat hut 98 d, H₂O 62.5 μg/mL He mycelium, rice, oat hut98 d, H₂O 125 μg/mL He mycelium, rice, oat hut 98 d, H₂O 250 μg/mL Hemycelium, rice, oat hut 98 d, EtOH 31.3 μg/mL He mycelium, rice, oat hut98 d, EtOH 62.5 μg/mL He mycelium, rice, oat hut 98 d, EtOH 125 μg/mL Hemycelium, rice, oat hut 98 d, EtOH 250 μg/mL He mycelium, rice, oat hut98 d, EtOAc 31.3 μg/mL He mycelium, rice, oat hut 98 d, EtOAc 62.5 μg/mLHe mycelium, rice, oat hut 98 d, EtOAc 125 μg/mL He mycelium, rice, oathut 98 d, EtOAc 250 μg/mL He fruiting body, H₂O 31.3 μg/mL He fruitingbody, H₂O 62.5 μg/mL He fruiting body, H₂O 62.5 μg/mL He fruiting body,H₂O 125 μg/mL He fruiting body, H₂O 250 μg/mL He fruiting body, EtOH31.3 μg/mL He fruiting body, EtOH 62.5 μg/mL He fruiting body, EtOH 125μg/mL He fruiting body, EtOH 250 μg/mL He fruiting body, EtOAc 31.3μg/mL He fruiting body, EtOAc 62.5 μg/mL He fruiting body, EtOAc 125μg/mL He fruiting body, EtOAc 250 μg/mL He mycelium, 193 d, EtOAc 31.3μg/mL He mycelium, 198 d, EtOAc 62.5 μg/mL He mycelium, 198 d, EtOAc 125μg/mL He mycelium, 198 d, EtOAc 250 μg/mL baeocystin 0.3 μg/mLbaeocystin 1 μg/mL baeocystin 3 μg/mL baeocystin 10 μg/mL norbaeocystin0.3 μg/mL norbaeocystin 1 μg/mL norbaeocystin 2 μg/mL norbaeocystin 10μg/mL norpsilocin 0.3 μg/mL norpsilocin 1 μg/mL norpsilocin 3 μg/mLnorpsilocin 10 μg/mL He mycelium 62.5 μg/mL + baeocystin 0.3 μg/mL Hemycelium 125 μg/mL + baeocystin 0.3 μg/mL He mycelium 62.5 μg/mL +baeocystin 1 μg/mL He mycelium 125 μg/mL + baeocystin 1 μg/mL Hemycelium 62.5 μg/mL + norbaeocystin 0.3 μg/mL He mycelium 125 μg/mL +norbaeocystin 0.3 μg/mL He mycelium 62.5 μg/mL + norbaeocystin 1 μg/mLHe mycelium 125 μg/mL + norbaeocystin 1 μg/mL He mycelium 62.5 μg/mL +norpsilocin 0.3 μg/mL He mycelium 125 μg/mL + norpsilocin 0.3 μg/mL Hemycelium 62.5 μg/mL + norpsilocin 1 μg/mL He mycelium 125 μg/mL +norpsilocin 1 μg/mL

Experiments were Conducted by Neurofit Contract Research Organization inIllkirch-Graffenstaden, France.

Rat Induced Pluripotent Stem Cell (iPSC) Neuron Culture CryopreservediCell neurons were thawed and plated according to instructions from theprovider (Cellular Dynamics International). The treatments were carriedout 2 h after the cell plating. The cells were maintained in ahumidified incubator at 37° C. in a 5% CO₂ atmosphere.

The following protocol was performed for each independent culture. Sixculture experiments were performed for each condition.

Day Procedure 0 Primary cultures of cortical neurons from rat embryowere initiated; Treatment with test compounds 3 Re-treatment with testcompounds 7 Re-treatment with test compounds 10 Evaluated neuritenetwork growth in tubulin immunostained neurons

Each culture plate contained a negative and positive control condition.Cells were treated with vehicle (negative control), 50 ng/mLbrain-derived neurotrophic factor (BDNF) (positive control), or thedifferent test compositions at the four different doses.

Evaluation of Neurite Outgrowth and Length

After ten days of culturing, the cultures were fixed with 4%paraformaldehyde in PBS. The cells were successively permeabilized,saturated with PBS containing 3% w/v bovine serum albumin (BSA) andincubated for 1 h with anti-beta Ill tubulin antibody (Sigma) diluted at1/10000 in PBS containing 0.5% of BSA. Cells wre first washed and arethen were incubated for 1 h with goat anti-mouse antibody coupled withAF488 (Invitrogen Δ11001) diluted at 1/1000 in PBS containing 0.5% ofBSA. Finally, nuclei are stained with DAPI 1 mg/mL at 1/1000 in PBScontaining 0.5% of BSA. After rinsing the cells with PBS, the plate isimaged and neurite networks are examined and analyzed using High-ContentScreening (CellInsight, Thermo Scientific Inc.).

Results are expressed as mean (±Standard Deviation). Statisticalanalyses of the data were performed using one-way analysis of variance(ANOVA). Where applicable, Fisher's PLSD test was used for multiplepairwise comparisons. The level of significance is set at p-value lessor equal to 0.05.

The evaluation of neurite outgrowth is performed using the averagenumber of neurites per neuron and the average of total neurite lengthper neuron. Data is shown in Table 5. Tables 6-9 show selections of datafrom Table 5 that includes the neurite length % of control data plottedin FIG. 1-3. Norpsilocin as a single compound did not perform betterthan vehicle control in this experiment at these concentrations.Surprisingly, the most pronounced neurite outgrowth was produced bycombining lion's mane extract (HE Myc) with norpsilocin suggesting thatHE Myc and norpsilocin work together synergistically to produce anincreased effect on neurite outgrowth (FIG. 3). Generally, the lowerconcentration ranges tended to produce the most significant impact onneurite length.

TABLE 5 Results of Neurite Outgrowth and Length Neurites per neuronNeurite length per neuron Number % of control Length (μm) % of controlStd. Std. Std. Std. Composition/Control Avg. Dev. Avg. Dev. Avg. Dev.Avg. Dev. Vehicle 3.24 0.12 100.00 3.79 364.93 52.46 100.00 14.38 BDNF50 ng/mL 3.32 0.14 117.76 4.43 528.55 55.31 144.84 15.16 He mycelium,rice 12 d, H2O 3.04 0.13 93.81 3.89 369.32 39.43 101.20 10.80 31.3 μg/mLHe mycelium, rice 12 d, H2O 2.76 0.14 85.07 4.43 318.27 47.44 87.2113.00 62.5 μg/mL He mycelium, rice 12 d, H2O 2.62 0.24 80.78 7.53 243.5726.04 66.74 7.13 125 μg/mL He mycelium, rice 12 d, H2O 1.56 0.12 48.183.62 90.61 7.14 24.83 1.96 250 μg/mL He mycelium, rice 12 d, 2.66 0.4732.08 14.40 277.26 89.32 75.97 24.48 EtOH 31.3 μg/mL He mycelium, rice12d, 3.00 0.12 92.65 3.80 329.45 18.81 90.28 5.15 EtOH 162.5 μg/mL Hemycelium, rice 12d, 2.60 0.14 80.16 4.43 213.46 19.25 58.49 5.27 EtOH125 μg/mL He mycelium, rice 12d, 0.68 0.25 21.07 7.72 30.88 12.12 8.463.32 EtOH 250 μg/mL Vehicle 3.29 0.06 100.00 1.85 373.68 33.23 100.003.39 BDNF 50 ng/mL 3.91 0.12 119.01 3.60 562.36 34.91 150.49 9.34 Hemycelium, rice 12 d, 3.03 0.13 92.14 3.92 419.95 34.28 112.38 9.17 EtOAc31.3 μg/mL He mycelium, rice 12 d, 2.91 0.10 88.46 2.98 385.38 48.34103.13 12.94 EtOAc 62.5 μg/mL He mycelium, rice 12 d, 2.74 0.09 83.342.62 345.61 50.36 92.49 13.48 EtOAc 125 μg/mL He mycelium, rice 12 d,2.72 0.07 82.85 2.24 325.09 18.75 87.00 5.02 EtOAc 250 μg/mL Hemycelium, rice, oat hull 2.89 0.07 88.05 2.07 337.17 47.14 90.23 12.6121 d, H2O 31.3 μg/mL He mycelium, rice, oat hull 2.79 0.09 34.91 2.60233.48 28.88 75.36 7.73 21 d, H2O 62.5 μg/mL He mycelium, rice, oat hull2.28 0.24 69.26 7.27 179.62 27.35 48.07 7.32 21 d, H2O 125 μg/mL Hemycelium, rice, oat hull 0.84 0.17 25.54 5.17 34.78 8.46 9.31 2.26 21 d,H2O 250 μg/mL Vehicle 3.21 0.19 100.00 5.85 328.29 45.85 100.00 13.97BDNF 50 μg/mL 3.84 0.13 119.47 4.09 518.78 40.30 158.03 12.28 Hemycelium, rice, oat hull 3.04 0.07 94.73 2.14 380.02 26.71 115.76 8.1421 d, EtOH 31.3 μg/mL He mycelium, rice, oat hull 2.93 0.14 91.08 4.43330.07 34.42 100.54 10.48 21 d, EtOH 62.5 μg/mL He mycelium, rice, oathull 2.73 0.19 34.97 5.95 244.31 27.01 74.42 8.23 21 d, EtOH 125 μg/mLHe mycelium, rice, oat hull 1.13 0.20 35.16 6.24 56.72 9.90 17.28 3.0221 d, EtOH 250 μg/mL He mycelium, rice, oat hull 2.78 0.12 86.54 3.86344.39 16.14 104.90 4.92 21 d, EtOAc 31.3 μg/mL He mycelium, rice, oathull 2.71 0.14 84.22 4.47 314.55 22.29 95.82 6.79 21 d, EtOAc 62.5 μg/mLHe mycelium, rice, oat hut 2.46 0.10 76.60 3.11 231.09 16.44 70.39 5.0121 d, EtOAc 125 μg/mL He mycelium, rice, oat hull 21 d, EtOAc 250 μg/mL1.46 0.24 45.53 7.38 81.91 19.16 24.95 5.34 Vehicle 3.34 0.09 100.002.74 337.25 44.13 100.00 13.08 BDNF 50 ng/mL 3.92 0.09 117.30 2.78506.15 51.13 150.08 15.16 He mycelium, rice, oat hull 2.93 0.10 87.583.00 333.12 54.38 98.78 16.13 98 d, H2O 31.3 μg/mL He mycelium, rice,oat hull 2.45 0.13 73.23 4.00 271.77 24.09 80.59 7.14 98 d, H2O 62.5μg/mL He mycelium, rice, oat hull 1.41 0.15 42.15 4.59 80.72 18.35 23.935.44 93 d, H2O 125 μg/mL He mycelium, rice, oat hull 98 d, H2O 250 μg/mL0.70 0.07 20.79 2.15 19.12 2.00 5.67 0.59 He mycelium, rice, oat hull3.06 0.23 91.60 6.95 345.99 47.76 102.59 14.16 98 d, EtOH 31.3 μg/mL Hemycelium, rice, oat hull 2.93 0.17 87.68 5.02 302.99 20.20 89.84 5.99 98d, EtOH 62.5 μg/mL He mycelium, rice, oat hull 0.46 0.13 13.62 3.9925.51 11.91 7.56 3.53 98 d, EtOH 125 μg/mL He mycelium, rice, oat hull98 d, EtOH 250 μg/mL 0.10 0.04 2.95 1.22 1.72 0.98 0.51 0.29 Vehicle3.31 0.05 100.00 1.40 366.88 49.52 100.00 13.50 BDNF 50 ng/mL 3.83 0.12115.54 3.71 522.46 48.31 142.40 13.17 He mycelium, rice, oat hull 3.070.07 92.66 2.23 407.96 38.10 111.19 10.33 98 d, EtOAc 31.3 μg/mL Hemycelium, rice, oat hull 3.17 0.10 95.64 2.98 421.18 14.05 114.80 3.8398 d, EtOAc 62,5 μg/mL He mycelium, rice, oat hull 2.93 0.03 38.36 2.48331.54 35.84 90.37 9.77 98 d, EtOAc 125 μg/mL He mycelium, rice, oathull 0.14 0.05 4.26 1.54 6.31 7.55 1.72 2.06 93 d, EtOAc 250 μg/mL Hefruiting body, H2O 31.3 2.92 0.09 88.22 2.61 339.52 61.06 92.54 16.64μg/mL He fruiting body, H2O 62.5 2.85 0.13 86.08 4.06 329.39 53.90 89.7814.69 μg/mL He fruiting body. H2O 125 2.86 0.05 86.28 1.54 280.77 19.3176.53 5.26 μg/mL He fruiting body, H2O 250 1.52 0.27 45.96 8.24 88.3817.68 24.09 4.82 μg/mL Vehicle 3.18 0.12 100.00 3.71 363.68 52.28 100.0014.37 BDNF 50 ng/mL 3.72 0.15 116.93 4.72 468.09 61.98 128.71 17.04 Hefruiting body, EtOH 31.3 2.91 0.10 91.59 3.01 358.36 63.57 98.53 17.48μg/mL He fruiting body, EtOH 62.5 2.69 0.23 84.74 7.13 331.97 93.6891.28 25.76 μg/mL He fruiting body, EtOH 125 2.76 0.18 86.71 5.68 359.0870.83 98.74 19.47 μg/mL He fruiting body, EtOH 250 2.55 0.23 30.29 7.28277.97 64.75 76.43 17.80 μg/mL He fruiting body, EtOAc 31.3 2.90 0.0491.28 1.20 349.19 7201. 96.02 19.80 μg/mL He fruiting body, EtOAc 62.52.94 0.17 92.61 5.48 376.15 58.62 103.43 16.12 μg/mL He fruiting body,EtOAc 125 2.97 0.18 93.59 5.80 349.24 66.57 96.03 18.30 μg/mL Hefruiting body. EtOAc 250 1.12 0.41 35.24 13.01 68.32 44.12 18.79 12.13μg/mL Vehicle 3.16 0.12 100.00 3.81 350.81 17.64 100.00 5.03 BDNF 50ng/mL 3.74 0.14 118.17 4.37 522.96 47.79 149.07 13.62 He mycelium, 198d, EtOAc 2.20 0.13 69.70 3.96 362.62 52.91 103.37 15.03 31.3 μg/mL Hemycelium, 198 d, EtOAc 0.07 0.02 2.16 0.67 1.34 0.32 0.38 0.09 62.5μg/mL He mycelium, 193 d, EtOAc 0.49 0.84 15.34 26.47 30.91 49.75 8.8114.18 125 μg/mL He mycelium, 198 d, EtOAc 0.06 0.05 2.02 1.65 1.64 1.120.47 0.32 250 μg/mL baeocystin 0.3 μg/mL 2.99 0.06 94.46 1.92 418.302203. 119.24 6.28 baeocystin 1 μg/mL 2.96 0.10 93.66 3.21 394.11 47.14112.34 13.44 baeocystin 3 μg/mL 3.07 0.10 97.18 3.23 415.42 55.25 118.4215.75 baeocystin 10 μg/mL 3.06 0.12 96.87 3.81 384.52 43.27 109.61 12.33Vehicle 3.34 0.18 100.00 5.43 343.36 51.31 100.00 14.94 BDNF 50 μg/mL3.80 0.23 113.92 6.83 510.71 88.59 148.74 25.80 norbaeocystin 0.3 μg/mL3.09 0.07 92.67 2.18 441.86 39.02 128.69 11.36 norbaeocystin 1 μg/mL3.06 0.10 91.64 2.99 436.93 34.89 127.25 10.16 norbaeocystin 3 μg/mL2.90 0.07 87.02 2.11 385.00 42.74 112.13 12.45 norbaeocystin 10 μg/mL3.07 0.14 92.01 4.20 386.86 27.40 112.67 7.98 norpsilocin 0.3 μg/mL 2.800.38 83.77 11.39 344.09 58.88 107.70 4.15 norpsilocin 1 μg/mL 2.91 0.1987.18 5.71 347.25 35.93 101.13 10.46 norpsilocin 3 μg/mL 2.65 0.34 79.3610.16 253.40 43.87 73.80 12.78 norpsilocin 10 μg/mL 0.92 0.31 27.71 9.1826.28 10.58 7.65 3.08 Vehicle 3.16 0.13 100.00 4.05 332.48 37.69 100.0011.34 BDNF 50 μg/mL 3.78 0.09 119.83 2.95 501.08 39.32 150.71 11.83 Hemycelium 62.5 μg/mL + 3.01 0.14 95.47 4.29 397.38 36.35 119.52 10.93baeocystin 0.3 μg/mL He mycelium 125 μg/mL + 2.67 0.08 84.62 2.47 257.7929.48 77.53 8.87 baeocystin 0.3 μg/mL He mycelium 62.5 μg/mL + 2.78 0.1188.12 3.40 310.54 25.97 93.40 7.81 baeocystin 1 μg/mL He mycelium 125μg/mL + 0.06 0.03 1.87 0.87 1.47 1.01 0.44 0.30 beeocystin 1 μg/mL Hemycelium 62.5 μg/mL + 2.98 0.10 94.30 3.32 329.72 19.82 99.17 5.96norbaeocystin 0.3 μg/mL He mycelium 125 μg/mL + 2.07 0.21 65.48 6.71267.64 45.96 80.50 13.82 norbaeocystin 0.3 μg/mL He mycelium 62.5μg/mL + 3.06 0.06 96.84 1.93 354.91 27.14 106.75 8.16 norbaeocystin 1μg/mL He mycelium 125 μg/mL + 2.61 0.14 32.74 4.32 231.75 37.26 69.7011.21 norbaeocystin 1 μg/mL Vehicle 3.00 0.16 100.00 5.28 295.88 63.27100.00 21.38 BDNF 50 μg/mL 3.81 0.12 127.06 3.93 568.90 44.08 192.2714.90 He mycelium 62.5 μg/mL + 3.07 0.16 102.43 5.27 403.20 33.36 136.2711.28 norpsilocin 0.3 μg/mL He mycelium 125 μg/mL + 2.06 0.07 68.81 2.46335.41 28.34 113.36 9.58 norpsilocin 0.3 μg/mL He mycelium 62.5 μg/mL +2.81 0.21 93.60 7.08 298.51 54.51 100.89 18.42 norpsilocin 1 μg/mL Hemycelium 125 μg/mL + 2.58 0.11 85.93 3.77 234.16 31.58 79.14 10.67norpsilocin 1 μg/mL

TABLE 6 Neurite Outgrowth and Length Neurites per neuron Neurite lengthper neuron Number % of control Length (μm) % of control Std. Std. Std.Std. Composition Avg. Dev. Avg. Dev. Avg.. Dev. Avg. Dev. baeocystin 0.3μg/mL 2.99 0.06 94.46 1.92 418.30 22.03 119.24 6.28 baeocystin 1 μg/mL2.96 0.10 93.66 3.21 394.11 47.14 112.34 13.44 baeocystin 3 μg/mL 3.070.10 97.18 3.23 415.42 55.25 118.42 15.75 baeocystin 10 μg/mL 3.06 0.1296.87 3.81 384.52 43.27 109.61 12.33 norbaeocystin 0.3 μg/mL 3.09 0.0792.67 2.18 441.86 39.02 128.69 11.36 norbaeocystin 1 μg/mL 3.06 0.1091.64 2.99 436.93 34.89 127.25 10.16 norbaeocystin 3 μg/mL 2.90 0.0787.02 2.11 385.00 42.74 112.13 12.45 norbaeocystin 10 μg/mL 3.07 0.1492.01 4.20 386.86 27.40 112.67 7.98 norpsilocin 0.3 μg/mL 2.80 0.3883.77 11.39 344.09 58.88 107.70 4.15 norpsilocin 1 μg/mL 2.91 0.19 87.185.71 347.25 35.93 101.13 10.46 norpsilocin 3 μg/mL 2.65 0.34 79.36 10.16253.40 43.87 73.80 12.78 norpsilocin 10 μg/mL 0.92 0.31 27.71 9.18 26.2810.58 7.65 3.08

TABLE 7 Neurite Outgrowth and Length Neurites per neuron Neurite lengthper neuron Number % of control Length (μm) % of control Std. Std. Std.Std. Composition Avg. Dev. Avg. Dev. Avg. Dev. Avg. Dev. He mycelium,rice 12 d, H2O 3.04 0.13 93.81 3.89 369.32 39.43 101.20 10.80 31.3 μg/mLHe mycelium, rice 12 d, 3.03 0.13 92.14 3.92 419.95 34.28 112.38 9.17EtOAc 31.3 μg/mL He mycelium, rice 12 d, 2.91 0.10 88.46 2.98 385.3848.34 103.13 12.94 EtOAc 62.5 μg/mL He mycelium, rice, cat hull 3.040.07 94.73 2.14 330.02 26.71 115.76 8.14 21 d, EtOH 31,3 μg/mL Hemycelium, rice, oat hull 2.78 0.12 86.54 3.86 344.39 16.14 104.90 4.9221 d, EtOAc 31.3 μg/mL He mycelium, rice, oat hull 3.06 0.23 91.60 6.95345.99 47.76 102.59 14.16 98 d, EtOH 31.3 μg/mL He mycelium, rice, oathull 3.07 0.07 92.66 2.23 407.96 38.10 111.19 10.38 98 d, EtOAc 31.3μg/mL He mycelium, rice, cat hull 3.17 0.10 95.64 2.98 421.18 14.05114.80 3.83 98 d, EtOAc 62.5 μg/mL He fruiting body. EtOAc 62.5 2.940.17 92.61 5.48 376.15 58.62 103.43 16.12 μg/mL He mycelium, 193 d,EtOAc 2.20 0.13 69.70 3.96 362.62 52.91 103.37 15.08 31.3 μg/mL

TABLE 8 Neurite Outgrowth and Length Neurites per neuron Neurite lengthper neuron Number % of control Length (μm) % of control Std. Std. Std.Std. Composition Avg. Dev. Avg. Dev. Avg. Dev. Avg. Dev. He mycelium,rice, oat hull 3.17 0.10 95.64 2.98 421.18 14.05 114.80 3.33 98 d, EtOAc62.5 μg/mL Norpsilocin 0.3 μg/mL 2.80 0.38 83.77 11.39 344.09 58.88107.70 4.15 He mycelium 62.5 μg/mL + 3.07 0.16 102.43 5.27 403.20 33.36136.27 11.28 norpsilocin 0.3 μg/mL Theoretical Additive Effect 2.6279.41 424.97 122.49

TABLE 9 Neurite Outgrowth and Length Neurites per neuron Neurite lengthper neuron Number % of control Length (μm) % of control Std. Std. Std.Std. Dev. Dev. Dev. Dev. Avg. Std. Avg. Std. Avg. Std. Avg. Std.Composition Avg. Dev. Avg. Dev. Avg. Dev. Avg. Dev. He mycelium, rice,oat hull 3.17 0.10 95.64 2.98 421.18 14.05 114.80 3.33 98 d, EtOAc 62.5μg/mL Norbaeocystin 0.3 μg/mL 3.09 0.07 92.67 2.18 441.86 39.02 128.6911.36 He mycelium 62.5 μg/mL + 2.98 0.10 94.30 3.32 329.72 19.82 99.175.96 norbaeocystin 0.3 μg/mL Theoretical Additive Effect 2.92 88.32522.74 143.49

TABLE 10 Neurite Outgrowth and Length Neurites per neuron Neurite lengthper neuron Number % of control Length (μm) % of control Std. Std. Std.Std. Composition Avg. Dev. Avg. Dev. Avg. Dev. Avg. Dev. He mycelium,rice, oat hull 3.17 0.10 95.64 2.98 421.18 14.05 114.80 3.83 98 d, EtOAc62.5 μg/mL Baeocystin 0.3 μg/mL 2.99 0.06 94.46 1.92 418.30 22.03 119.246.28 He mycelium 62.5 μg/mL + 3.01 0.14 95.47 4.29 397.38 36.35 119.5210.93 baeocystin 0.3 μg/mL Theoretical Additive Effect 2.81 90.10 499.18134.04

Example 3

Neurite Outgrowth 4 (NO-4) produced statistically significant hits forseveral HE extracts as well as each psilocybin analog tested in theassay. Subsequently, Neurite Outgrowth 5 tested for potentialsynergistic effects from combining HE extracts with pure compounds. Thetreatments were comparable to those of NeuroFit2, aiming to determine ifpotential synergistic effects identified by NeuroFit were reproduciblein-house.

PC12 cells were grown to confluency in a 96 well plate, starved, andtreated with HE 98d EtOAc mycelium extract, psilocybin analogs, orHE-analog stacks (FIG. 6). Culture media was refreshed after day 7.Images were taken at days 5, 7, and 11 and were then analyzed forneurite length via ImageJ. Images were taken at 20× and focused on themost prominent instances of neurite outgrowth in each well.

Generally, the data from NO-5 largely reflect those of NO-4, and onceagain, statistically significant hits were identified for HE andpsilocybin analogs. At all time points, the 31.25 μg/mL HE extractsproduced the strongest neurite outgrowth, having the greatest meanneurite length of any statistically significant treatment (FIGS. 7, 8,9). Day 7 produced the strongest neurite outgrowth as all treatmentstended have the longest mean neurite length at this time point (FIG.10).

As observed with the previous assay, NO-5 provides further validation ofin-house cell culture capabilities and demonstrates that the neuriteoutgrowth assay can be simplified by applying compounds directly to PC12cells. Refreshing culture media did not produce a noticeable neuritelength benefit to PC12 cells, as the day 11 treatment still appeared tohave some reduction in neurite length when compared to day 7. However,at day 11 statistically significant hits were produced for all threepsilocybin analogs.

Although the assay aimed to explore potential synergistic effects ofcombining HE and psilocybin analogs, this was not clearly observed. Thisis largely due to the 31.25 μg/mL HE extract outperforming any otherindividual or stacked treatment at days 5, 7, and 11. In this assay, the31.25 μg/mL HE extract produced strong neurite outgrowth at a lowerdosage than previously observed, likely due to this fresh extract beingmore concentrated. Overall, these data provide increased confidence inthe role of lion's mane extracts and psilocybin analogs in inducingneurite outgrowth both in-house and from third party assays. 1321N1human brain astrocytoma cells are known to excrete neurologicallybeneficial compounds when stimulated with neurotrophic compounds andfungal extracts including lion's mane (Mori et al., Biological andPharmaceutical Bulletin, 9: 1727-1732 (2008)). While some fungi havewell established mechanisms by which they benefit neurological health,little is known about the role of psilocybin analogs specifically.Generally following the protocol of Mori et al., 2008, 1321N1 humanastrocytoma cells were treated with psilocybin analogs, and conditionedmedia was collected and applied to differentiated rat pheochromocytomaPC12 cells to determine the resulting impact on neurite outgrowth.Conditioned media from baeocystin, norbaeocystin, and norpsilocin werefound to induce neurite outgrowth in PC12 cells, suggesting thatpsilocybin analogs induce the expression and secretion of neurologicallybeneficial compounds, potentially including nerve growth factor (NGF)(FIG. 11). When PC12 cells were directly treated with psilocybinanalogs, comparable effects were observed at several time points (FIG.9).

Example 4

Mitogen-activated protein kinases (MAPKs) provide a wide-rangingsignaling cascade that allow cells to quickly respond to biotic andabiotic stimuli. The objective of this project was to determine if HEextracts from Fungi Perfecti (FP) impact MAPKs (e.g., influence theexpression and phosphorylation of various MAPKs—notably JNK, c-Jun, andc-fos—to promote nerve growth factor (NGF) expression). Here, four FPextracts were tested at three concentrations each (Table 11). Theseextracts were tested against five MAPKs: c-Jun N-terminal kinase 1-3(JNK, JNK2, JNK3), Rho Associated Coiled-Coil Containing Protein KinasesT and 2 (ROCK, ROCK2), and tropomyosin receptor kinase B (TRKB).Collectively, these MAPKs are major players in neural health,influencing neurogenesis, neural growth and differentiation, andneurodegenerative diseases.

TABLE 11 Concentrations of FP HE extracts tested for binding to MAPKtargets Extract Concentrations Tested (μg/mL) HD HE Extract 62.5 125 250HE EtOAc 62.5 125 250 HE Water Wash 62.5 125 250 HD Powder 31.25 62.5125 HD: Host Defense ® Lion's Mane (Hericium erinaceus) product (FungiPerfecti)

While several potential MAPK hits were identified for all extracts, theHost Defense (Fungi Perfecti; “HO”) HE EtGH and HE EtOAc extractselicited the most pronounced impacts, particularly the latter extract(FIG. 12). (Note: based on the % Control kinase binding calculation,stronger hits are represented by lower values.)

Interestingly, the top two hits included the HE EtOAc extract on JNK3and the HO HE EtOH extract with ROCK1 (Table 12). This suggests that theextraction method may play a significant role in the ways in whichneural health is impacted. While the strongest MAPK impact was found onJNK3 with the EtOAc extract, the EtOH extract did not produce a strongimpact on this specific kinase. This may be due to the EtOAc extractionmethod producing the strongest detectable erinacine content.

TABLE 12 Top ten hits identified in the MAPK binding assay DiscoveRxEntrez Compound Compound Gene Gene Percent Conc. Name Symbol SymbolControl (μg/mL) HE EtOAc JNK3 MAPK10 54 250 HD Extract ROCK1 ROCK1 65250 HE EtOAc JNK2 MAPK9 70 250 HE EtOAc ROCK1 ROCK1 73 250 HD ExtractROCK2 ROCK2 74 250 HE EtOAc JNK3 MAPK10 74 125 HE EtOAc JNK1 MAPK8 74250 HE EtOAc ROCK2 ROCK2 76 250 HE Water Wash JNK1 MAPK8 76 250 HE EtOAcJNK2 MAPK9 78 62.5 HD: Host Defense ® Lion's Mane (Hericium erinaceus)product (Fungi Perfecti)

Collectively, MAPK binding data suggest that FP HE extracts impactneural health on several broad levels. Of the top MAPKs impacted by HEextracts, the JNKs play a role in cell degeneration, while the ROCKsplay a role in cell survival. Accordingly, FP HE extracts may play animmunomodulatory role in influencing immune system homeostasis (FIG.13).

Contrary to results from neurite outgrowth cellular assays, higherextract concentrations in MAPK binding assays tended to elicit astronger response. At 250 μg/mL, the EtOAc had a strong impact on thebinding of TRKB, a well-characterized, high affinity receptor ofbrain-derived neurotrophic factor (BDNF), further broadening the scopeat which FP HE extracts modulate neural activity.

Ultimately, findings from the MAPK binding assays strengthen themechanisms by which FP HE extracts influence neurogenic activity. Inaddition to morphology-based cellular assays in several cell lines,there is now evidence that FP extracts are driving neurite growththrough diverse, classical neurogenic pathways related to neurotrophicfactors including both NGF and BDNF.

The ability of psilocybin analogs to stimulate neurite outgrowth isdemonstrated in several cell models. Accordingly, preliminary researchhas started to reveal the mechanisms by which psilocybin analogs mayconfer neurotrophic benefits that facilitate neurite outgrowth. Human1321N1 brain cells treated with norbaeocystin have increased expressionof NGF protein when compared to a vehicle control (FIG. 16).

Example 5

Microdosing with dried psilocybin mushrooms (presumption: Psilocybecubensis) in humans was used to study the effects of psilocybinmushrooms on depression, anxiety, and mood. The data was collected usinganonymous self-reporting through a phone app (microdose.me). 16% ofrespondents reported using a low dose (<0.10 grams), 72% of respondentsreported using a medium dose (0.10-0.30 grams), and 12% of respondentsreported using a high dose (>30 grams). The large study sample included8703 participants at baseline with 3,486 psilocybin users, 447 LSDusers, 117 other (46.5% were microdosers). A subsample of the largesample included 159 participants that started microdosing psilocybinwith 1-month FU (28% female) and 83 participants that werenon-microdosers (19% female). Among microdosers, 22% dosed <2×/wk, 47%dosed 2-4×/wk, and 29% dosed >4×/wk. Microdosing was correlated withdecreased depression and anxiety as compared to non-microdosers (FIG.17) and increased positive mood as compared to non-microdosers (FIG.18). Stacking psilocybin mushrooms with Lion's Mane mushrooms did notincrease the effect on depression or positive mood as compared topsilocybin mushrooms alone (FIG. 19). Positive effects were equivalentamong those who stacked with Lion's Mane (with and without niacin) andthose who did not stack. However, the data was collected after 4 weeksof administration and data has shown that Lion's Mane, when used inclinical studies, increased cognition at 8, 12 and 16 weeks. Therefore,the psilocybin and Lion's Mane stack may work synergistically to treatdepression and anxiety and increase positive mood when used incombination for greater than 4 weeks. Overall, microdosing psilocybinwas associated with reduced depression and improved mood at 1 month.Effects for depression were in the medium range: η2=0.05/d=0.5, whereasSSRIs are in the d=0.3 range. It is notable that this is a non-clinicalpopulation. Effects for positive mood were large−η2=0.13/d=0.8.

Example 6

Pochonia chlamydosporia is a fungal egg parasite of root-knot and cystnematodes. It colonizes in the roots of several plant species and caninduce plant defense mechanisms and local resistance infungal-nematode-plant interactions. It has also been shown that Pochoniachlamydosporia can produce ketamine. Ferreira et al., Parasites &Vectors, 13:527 (2020). Pochonia chlamydosporia will be cocultured withpsilocybin-containing mushroom mycelia. Alternatively, Pochoniachlamydosporia will be cultured alone on a substrate such as a ricesubstrate and its mycelium will be inactivated or killed. Then,psilocybin-containing mushrooms will be cultivated upon the inactivated,ketamine producing mycelium and substrate. These growing conditions mayproduce novel alkaloids or medicines that may be used for treating orpreventing neuronal injuries, neurodegeneration, neurological diseases,congenital or organic cognitive impairment, learning disabilities,autism spectrum disorder, psychiatric and mood disorders, cognitiveenhancement, physical or motor neuron enhancement, or generalimprovement of mental health, inter alia.

The cultivated Pochonia chlamydosporia and/or psilocybin-containingmushrooms are frozen and ground and extracted in water for 2 h at roomtemperature. The extract is filtered through Whatman filter via gravity.The filtrate is lyophilized to dryness. Ethanol extracts are made fromthe same mycelium. The mycelium is frozen, but not ground, and extractedin 70% ethanol for 1 week at room temperature. The extract is filteredthrough an 80-mesh sieve and lyophilized to dryness. A portion of theethanol extract is rotovapped to dryness and the residue is resuspendedin 1:1 water:ethyl acetate. The water/ethyl acetate extract is washed 3times with ethyl acetate, the combined organic fractions dried overMgSO₄, filtered, rotovapped, and then lyophilized.

Additionally, Pochonia species and Psilocybe species (or otherpsilocybin producing fungi) can be co-cultured together in fermentationor on solid (“semi-solid media”) to create a quorum of two organismswhose active principle ingredients-such as ketamine or ketamine analogsfrom Pochnia and psilocybin/psilocin and psilocybin/psilocinanalogues—may be expressed, and subsequently harvested to create aunique combination.

At least 30 mg of psilocybin (0.5-1 mg/kg) is a strong dose, while 70 mgof ketamine 1.5 mg/kg (0.5-2.0 mg/kg) is a similarly strong psychedelicdose.

Experiments are conducted to evaluate the neurotrophic effects ofseveral purified tryptamines, H. erinaceum extracts combined withselected extracts of Pochonia chlamydosporia. The experiments analyzethe Pochonia chlamydosporia growth medium (rice, oat, straw, sawdust, orcombinations thereof), the days of cultivation, the extract solvent(water, ethanol, or ethyl acetate), and the final concentration of theextract. The following compositions are tested (Table 13):

TABLE 13 Test Compositions Pochonia chlamydosporia mycelium, rice 12 d,H₂O Pochonia chlamydosporia mycelium, oat 12 d, H₂O Pochoniachlamydosporia mycelium, straw 12 d, H₂O Pochonia chlamydosporiamycelium, sawdust 12 d, H₂O Pochonia chlamydosporia mycelium, rice 12 d,EtOH Pochonia chlamydosporia mycelium, oat 12 d, EtOH Pochoniachlamydosporia mycelium, straw 12 d, EtOH Pochonia chlamydosporiamycelium, sawdust 12 d, EtOH Pochonia chlamydosporia mycelium, rice 12d, EtOAc Pochonia chlamydosporia mycelium, oat 12 d, EtOAc Pochoniachlamydosporia mycelium, straw 12 d, EtOAc Pochonia chlamydosporiamycelium, sawdust 12 d, EtOAc Pochonia chlamydosporia mycelium, rice 21d, H₂O Pochonia chlamydosporia mycelium, oat 21 d, H₂O Pochoniachlamydosporia mycelium, straw 21 d, H₂O Pochonia chlamydosporiamycelium, sawdust 21 d, H₂O Pochonia chlamydosporia mycelium, rice 21 d,EtOH Pochonia chlamydosporia mycelium, oat 21 d, EtOH Pochoniachlamydosporia mycelium, straw 21 d, EtOH Pochonia chlamydosporiamycelium, sawdust 21 d, EtOH Pochonia chlamydosporia mycelium, rice 21d, EtOAc Pochonia chlamydosporia mycelium, oat 21 d, EtOAc Pochoniachlamydosporia mycelium, straw 21 d, EtOAc Pochonia chlamydosporiamycelium, sawdust 21 d, EtOAc Pochonia chlamydosporia mycelium, rice 98d, H₂O Pochonia chlamydosporia mycelium, oat 98 d, H₂O Pochoniachlamydosporia mycelium, straw 98 d, H₂O Pochonia chlamydosporiamycelium, sawdust 98 d, H₂O Pochonia chlamydosporia mycelium, rice 98 d,EtOH Pochonia chlamydosporia mycelium, oat 98 d, EtOH Pochoniachlamydosporia mycelium, straw 98 d, EtOH Pochonia chlamydosporiamycelium, sawdust 98 d, EtOH Pochonia chlamydosporia mycelium, rice 98d, EtOAc Pochonia chlamydosporia mycelium, oat 98 d, EtOAc Pochoniachlamydosporia mycelium, straw 98 d, EtOAc Pochonia chlamydosporiamycelium, sawdust 98 d, EtOAc Pochonia chlamydosporia mycelium, rice 198d, H₂O Pochonia chlamydosporia mycelium, oat 198 d, H₂O Pochoniachlamydosporia mycelium, straw 198 d, H₂O Pochonia chlamydosporiamycelium, sawdust 198 d, H₂O Pochonia chlamydosporia mycelium, rice 198d, EtOH Pochonia chlamydosporia mycelium, oat 198 d, EtOH Pochoniachlamydosporia mycelium, straw 198 d, EtOH Pochonia chlamydosporiamycelium, sawdust 198 d, EtOH Pochonia chlamydosporia mycelium, rice 198d, EtOAc Pochonia chlamydosporia mycelium, oat 198 d, EtOAc Pochoniachlamydosporia mycelium, straw 198 d, EtOAc Pochonia chlamydosporiamycelium, sawdust 198 d, EtOAc Pochonia chlamydosporia mycelium +psilocybin-containing mycelium, rice 12 d, H₂O Pochonia chlamydosporiamycelium + psilocybin-containing mycelium, oat 12 d, H₂O Pochoniachlamydosporia mycelium + psilocybin-containing mycelium, straw 12 d,H₂O Pochonia chlamydosporia mycelium + psilocybin-containing mycelium,sawdust 12 d, H₂O Pochonia chlamydosporia mycelium +psilocybin-containing mycelium, rice 12 d, EtOH Pochonia chlamydosporiamycelium + psilocybin-containing mycelium, oat 12 d, EtOH Pochoniachlamydosporia mycelium + psilocybin-containing mycelium, straw 12 d,EtOH Pochonia chlamydosporia rrlycelium + psilocybin-containingmycelium, sawdust 12 d, EtOH Pochonia chlamydosporia mycelium +psilocybin-containing mycelium, rice 12 d, EtOAc Pochonia chlamydosporiamycelium + psilocybin-containing myceliurn, oat 12 d, EtOAc Pochoniachlamydosporia mycelium + psilocybin-containing mycelium, straw 12 d,EtOAc Pochonia chlamydosporia mycelium + psilocybin-containing mycelium,sawdust 12 d, EtOAc Pochonia chlamydosporia mycelium +psilocybin-containing mycelium, rice 21 d, H₂O Pochonia chlamydosporiamycelium + psilocybin-containing mycelium, oat 21 d, H₂O Pochoniachlamydosporia mycelium + psilocybin-containing mycelium, straw 21 d,H₂O Pochonia chlamydosporia mycelium + psilocybin-containing mycelium,sawdust 21 d, H₂O Pochonia chlamydosporia mycelium +psilocybin-containing mycelium, rice 21 d, EtOH Pochonia chlamydosporiamycelium + psilocybin-containing mycelium, oat 21 d, EtOH Pochoniachlamydosporia mycelium + psilocybin-containing mycelium, straw 21 d,EtOH Pochonia chlamydosporia mycelium + psilocybin-containing mycelium,sawdust 21 d, EtOH Pochonia chlamydosporia mycelium +psilocybin-containing mycelium, rice 21 d, EtOAc Pochonia chlamydosporiamycelium + psilocybin-containing mycelium, oat 21 d, EtOAc Pochoniachlamydosporia mycelium + psilocybin-containing mycelium, straw 21 d,EtOAc Pochonia chlamydosporia mycelium + psilocybin-containing mycelium,sawdust 21 d, EtOAc Pochonia chlamydosporia mycelium +psilocybin-containing mycelium, rice 98 d, H₂O Pochonia chlamydosporiamycelium + psilocybin-containing mycelium, oat 98 d, H₂O Pochoniachlamydosporia mycelium + psilocybin-containing mycelium, straw 98 d,H₂O Pochonia chlamydosporia mycelium + psilocybin-containing mycelium,sawdust 98 d, H₂O Pochonia chlamydosporia mycelium +psilocybin-containing mycelium, rice 98 d, EtOH Pochonia chlamydosporiamycelium + psilocybin-containing mycelium, oat 98 d, EtOH Pochoniachlamydosporia mycelium + psilocybin-containing mycelium, straw 98 d,EtOH Pochonia chlamydosporia mycelium + psilocybin-containing mycelium,sawdust 98 d, EtOH Pochonia chlamydosporia mycelium +psilocybin-containing mycelium, rice 98 d, EtOAc Pochonia chlamydosporiamycelium + psilocybin-containing mycelium, oat 98 d, EtOAc Pochoniachlamydosporia mycelium + psilocybin-containing mycelium, straw 98 d,EtOAc Pochonia chlamydosporia mycelium + psilocybin-containing mycelium,sawdust 98 d, EtOAc Pochonia chlamydosporia mycelium +psilocybin-containing mycelium, rice 198 d, H₂O Pochonia chlamydosporiamycelium + psilocybin-containing mycelium, oat 198 d, H₂O Pochoniachlamydosporia mycelium + psilocybin-containing mycelium, straw 198 d,H₂O Pochonia chlamydosporia mycelium + psilocybin-containing mycelium,sawdust 198 d, H₂O Pochonia chlamydosporia mycelium +psilocybin-containing mycelium, rice 193 d, EtOH Pochonia chlamydosporiamycelium + psilocybin-containing mycelium, oat 198 d, EtOH Pochoniachlamydosporia mycelium + psilocybin-containing mycelium, straw 198 d,EtOH Pochonia chlamydosporia mycelium + psilocybin-containing mycelium,sawdust 198 d, EtOH Pochonia chlamydosporia mycelium +psilocybin-containing mycelium, rice 198 d, EtOAc Pochoniachlamydosporia mycelium + psilocybin-containing mycelium, oat 198 d,EtOAc Pochonia chlamydosporia mycelium + psilocybin-containing mycelium,straw 198 d, EtOAc Pochonia chlamydosporia mycelium +psilocybin-containing mycelium, sawdust 198 d, EtOAc InactivatedPochonia chlamydosporia mycelium + psilocybin-containing mycelium, rice12 d, H₂O Inactivated Pochonia chlamydosporia mycelium +psilocybin-containing mycelium, oat 12 d, H₂O Inactivated Pochoniachlamydosporia mycelium + psilocybin-containing mycelium, straw 12 d,H₂O Inactivated Pochonia chlamydosporia mycelium + psilocybin-containingmycelium, sawdust 12 d, H₂O Inactivated Pochonia chlamydosporiamycelium + psilocybin-containing mycelium, rice 12 d, EtOH InactivatedPochonia chlamydosporia mycelium + psilocybin-containing mycelium, oat12 d, EtOH Inactivated Pochonia chlamydosporia mycelium +psilocybin-containing mycelium, straw 12 d, EtOH Inactivated Pochoniachlamydosporia mycelium + psilocybin-containing mycelium, sawdust 12 d,EtOH Inactivated Pochonia chlamydosporia mycelium +psilocybin-containing mycelium, rice 12 d, EtOAc Inactivated Pochoniachlamydosporia mycelium + psilocybin-containing mycelium, oat 12 d,EtOAc Inactivated Pochonia chlamydosporia mycelium +psilocybin-containing mycelium, straw 12 d, EtOAc Inactivated Pochoniachlamydosporia mycelium + psilocybin-containing mycelium, sawdust 12 d,EtOAc Inactivated Pochonia chlamydosporia mycelium +psilocybin-containing mycelium, rice 21 d, H₂O Inactivated Pochoniachlamydosporia mycelium + psilocybin-containing mycelium, oat 21 d, H₂OInactivated Pochonia chlamydosporia mycelium + psilocybin-containingmycelium, straw 21 d, H₂O Inactivated Pochonia chlamydosporia mycelium +psilocybin-containing mycelium, sawdust 21 d, H₂O Inactivated Pochoniachlamydosporia mycelium + psilocybin-containing mycelium, rice 21 d,EtOH Inactivated Pochonia chlamydosporia mycelium +psilocybin-containing mycelium, oat 21 d, EtOH Inactivated Pochoniachlamydosporia mycelium + psilocybin-containing mycelium, straw 21 d,EtOH Inactivated Pochonia chlamydosporia mycelium +psilocybin-containing mycelium, sawdust 21 d, EtOH Inactivated Pochoniachlamydosporia mycelium + psilocybin-containing mycelium, rice 21 d,EtOAc Inactivated Pochonia chlamydosporia mycelium +psilocybin-containing mycelium, oat 21 d, EtOAc Inactivated Pochoniachlamydosporia mycelium + psilocybin-containing mycelium, straw 21 d,EtOAc Inactivated Pochonia chlamydosporia mycelium +psilocybin-containing mycelium, sawdust 21 d, EtOAc Inactivated Pochoniachlamydosporia mycelium + psilocybin-containing mycelium, rice 98 d, H₂OInactivated Pochonia chlamydosporia mycelium + psilocybin-containingmycelium, oat 98 d, H₂O Inactivated Pochonia chlamydosporia mycelium +psilocybin-containing mycelium, straw 98 d, H₂O Inactivated Pochoniachlamydosporia mycelium + psilocybin-containing mycelium, sawdust 98 d,H₂O Inactivated Pochonia chlamydosporia mycelium + psilocybin-containingmycelium, rice 98 d, EtOH Inactivated Pochonia chlamydosporia mycelium +psilocybin-containing mycelium, oat 98 d, EtOH Inactivated Pochoniachlamydosporia mycelium + psilocybin-containing mycelium, straw 98 d,EtOH Inactivated Pochonia chlamydosporia mycelium +psilocybin-containing mycelium, sawdust 98 d, EtOH Inactivated Pochoniachlamydosporia mycelium + psilocybin-containing mycelium, rice 98 d,EtOAc Inactivated Pochonia chlamydosporia mycelium +psilocybin-containing mycelium, oat 98 d, EtOAc Inactivated Pochoniachlamydosporia mycelium + psilocybin-containing mycelium, straw 98 d,EtOAc Inactivated Pochonia chlamydosporia mycelium +psilocybin-containing mycelium, sawdust 98 d, EtOAc Inactivated Pochoniachlamydosporia mycelium + psilocybin-containing mycelium, rice 198 d,H₂O Inactivated Pochonia chlamydosporia mycelium + psilocybin-containingmycelium, oat 198 d, H₂O Inactivated Pochonia chlamydosporia mycelium +psilocybin-containing mycelium, straw 198 d, KO Inactivated Pochoniachlamydosporia mycelium + psilocybin-containing mycelium, sawdust 198 d,H₂O Inactivated Pochonia chlamydosporia mycelium + psilocybin-containingmycelium, rice 198 d, EtOH Inactivated Pochonia chlamydosporiamycelium + psilocybin-containing mycelium, oat 198 d, EtOH InactivatedPochonia chlamydosporia mycelium + psilocybin-containing mycelium, straw198 d, EtOH Inactivated Pochonia chlamydosporia mycelium +psilocybin-containing mycelium, sawdust 198 d, EtOH Inactivated Pochoniachlamydosporia mycelium + psilocybin-containing mycelium, rice 198 d,EtOAc Inactivated Pochonia chlamydosporia mycelium +psilocybin-containing mycelium, oat 198 d, EtOAc Inactivated Pochoniachlamydosporia mycelium + psilocybin-containing mycelium, straw 198 d,EtOAc Inactivated Pochonia chlamydosporia mycelium +psilocybin-containing mycelium, sawdust 198 d, EtOAc Pochoniachlamydosporia fruiting body, H₂O Pochonia chlamydosporia fruiting body,EtOH Pochonia chlamydosporia fruiting body, EtOAc Pochoniachlamydosporia + baeocystin 0.3 μg/mL Pochonia chlamydosporia +baeocystin 1 μg/mL Pochonia chlamydosporia + norbaeocystin 0.3 μg/mLPochonia chlamydosporia + norbaeocystin 1 μg/mL Pochoniachlamydosporia + norpsilocin 0.3 μg/mL Pochonia chlamydosporia +norpsilocin 1 μg/mL Pochonia chlamydosporia fruiting body +psilocybin-containing fruiting body, H₂O Pochonia chlamydosporiafruiting body + psilocybin-containing fruiting body, EtOH Pochoniachlamydosporia fruiting body + psilocybin-containing fruiting body,EtOAc Pochonia chlamydosporia + psilocybin-containing mycelium +baeocystin 0.3 μg/mL Pochonia chlamydosporia + psilocybin-containingmycelium + baeocystin 1 μg/mL Pochonia chlamydosporia +psilocybin-containino mycelium + norbaeocystin 0.3 μg/mL Pochoniachlamydosporia + psilocybin-containing mycelium + norbaeocystin μg/mLPochonia chlamydosporia + psilocybin-containing mycelium + norpsilocin0.3 μg/mL Pochonia chlamydosporia + psilocybin-containing mycelium +norpsilocin 1 μg/mL Inactivated Pochonia chlamydosporia +psilocybin-containing mycelium + baeocystin 0.3 μg/mL InactivatedPochonia chlamydosporia + psilocybin-containino mycelium + baeocystin 1μg/mL Inactivated Pochonia chlamydosporia + psilocybin-containingmycelium + norbaeocystin 0.3 μg/mL Inactivated Pochonia chlamydosporia +psilocybin-containing mycelium + norbaeocystin 1 μg/mL InactivatedPochonia chlamydosporia + psilocybin-containing mycelium + norpsilocin0.3 μg/mL Inactivated Pochonia chlamydosporia + psilocybin-containingmycelium + norpsilocin 1 μg/mL

The compositions are tested for effects on neurite outgrowth andlengthening, MAPK signaling, NGF expression, depression, anxiety, andmood. The composition may be used in a microdosing regimen.

Example 7

This research has revealed distinct roles of psilocybin analogs inbenefiting neurological health. ELISA assays in human 1321N1 brain cellsfound that norbaeocystin induces the expression of nerve growth factor(NGF) protein while norpsilocin induces the expression of theanti-inflammatory cytokine IL-10. Moreover, Ly et al. found thatpsychedelic compounds are unable to induce the expression of BDNFtranscript, while we have observed strong induction of BDNF transcriptby lion's mane extract. See Ly et al., “Psychedelics Promote Structuraland Functional Neural Plasticity,” Cell Rep. 23: 3170-3182 (2018).Collectively, this suggests that the combination of psilocybin analogswith lion's mane benefits brain health in diverse and complementarymechanisms.

Neuroinflammatory consequences of COVID-19 infection, and that of otherneuroinflammatory viruses, causes a wide range of negative effects onhuman health and mental well-being. Since health and mental health areinextricably interrelated, there is a great need to resolve adverseeffects to the nervous system in general. In addition, activation of5-HT_(2A) receptors produces potent anti-inflammatory effects in animalmodels and are believed to block TNF-α induced inflammation. SeeFlanagan and Nichols, “Psychedelics and anti-inflammatory agents” Inter.Rev. Psychiatry 30(4): 363-375 (2018). Thus, the compositions describedherein may have synergistic benefits in reducing inflammation,increasing neurogenesis, and ameliorating mental health disorders orissues.

Further, high doses of tryptamines, particularly aeruginascin,4-hydroxy-N,N,N-trimethyltryptamine, or bufotenidine, maybe useful foranesthetic or neuroanesthetic applications. These compounds areassociated with the phenomenon “Wood Lover Paralysis,” a temporarymuscle weakness or paralysis that sometimes occurs several hours afterconsuming certain types of psilocybin mushrooms grown on decaying wood.

The unique combination, or norpsilocin alone, will have a significantimpact on the improvement of mental health and resolution oramelioration of a wide range of mental diseases. Such improvementsinclude increase in intelligence, cognition, mental state of being,mood, overcoming depression, overcoming PTSD, enhancing coordination,hearing, seeing or vision. Moreover, the combinations in this inventionmay positively impact and improve the neurological health of thosesuffering from Alzheimer's, multiple sclerosis, and other diseases thatare detrimental to human health as a consequence of neuroinflammation.

The methods and compositions that includes the combination ofnorbaeocystin to induce the expression of nerve growth factor (NGF)protein and norpsilocin to induce the expression of theanti-inflammatory cytokine IL-10.

The psilocybin analogs described herein have unique bindingcharacteristics with 5-HT receptors and can work synergistically to havegreater than the expected cumulative effects.

What is claimed:
 1. A composition comprising: a tryptamine,pharmaceutically acceptable salts, hydrates, or solvates thereof; and anextract of Hericium erinaceus.
 2. The composition of claim 1, furthercomprising niacin.
 3. The composition of claim 1, wherein the tryptamineis 4-hydroxytryptamine, 5-hydroxytryptamine (serotonin), aeruginascin,4-hydroxy-N,N,N-trimethyltryptamine, 5-hydroxy-N,N,N-trimethyltryptamine(bufotenidine), N-methyltryptamine, N-ethyltryptamine,N-methyl-N-ethyltryptamine, N-methyl-N-propyltryptamine,N,N-diethyltryptamine, N-methyl-N-isopropyltryptamine,N-ethyl-N-isopropyltryptamine, N,N-diisopropyltryptamine,N,N-dipropyltryptamine, N,N-diallyltryptamine, 4-hydroxytryptamine,4-hydroxy-N-methyltryptamine (norpsilocin),4-hydroxy-N-methyl-N-ethyltryptamine,4-hydroxy-N-methyl-N-propyltryptamine, 4-hydroxy-N,N-diethyltryptamine,4-hydroxy-N-ethyl-N-isopropyltryptamine,4-hydroxy-N,N-diisopropyltryptamine, 4-hydroxy-N,N-dipropyltryptamine,4-hydroxy-N,N-diallyltryptamine, 4-methoxytryptamine,4-methoxy-N-methyltryptamine (norpsilocin),4-methoxy-N-methyl-N-ethyltryptamine,4-methoxy-N-methyl-N-propyltryptamine, 4-methoxy-N,N-diethyltryptamine,4-methoxy-N-ethyl-N-isopropyltryptamine,4-methoxy-N,N-diisopropyltryptamine, 4-methoxy-N,N-dipropyltryptamine,4-methoxy-N—N-diallyltryptamine, 4-acetoxytryptamine,4-acetoxy-N-methyltryptamine, 4-acetoxy-N-methyl-N-ethyltryptamine,4-acetoxy-N-methyl-N-ethyltryptamine,4-acetoxy-N-methyl-N-propyltryptamine, 4-acetoxy-N,N-diethyltryptamine,4-acetoxy-N-methyl-N-isopropyltryptamine,4-acetoxy-N-ethyl-N-isopropyltryptamine,4-acetoxy-N,N-diisopropyltryptamine, 4-acetoxy-N—N-dipropyltryptamine,4-acetoxy-N—N-diallyltryptamine, 5-hydroxytryptamine,5-hydroxy-N-methyltryptamine, 5-hydroxy-N,N-dimethyltryptamine(bufotenine), 5-hydroxy-N-methyl-N-ethyltryptamine,5-hydroxy-N-methyl-N-propyltryptamine, 5-hydroxy-N,N-diethyltryptamine,5-hydroxy-N-methyl-N-isopropyltryptamine,5-hydroxy-N-ethyl-N-isopropyltryptamine,5-hydroxy-N,N-diisopropyltryptamine, 5-hydroxy-N,N-dipropyltryptamine,5-hydroxy-N—N-dipropyltryptamine, 5-hydroxy-N—N-diallyltryptamine,5-methoxytryptamine, 5-methoxy-N-methyltryptamine,5-methoxy-N,N-dimethyltryptamine, 5-methoxy-N-methyl-N-ethyltryptamine,5-methoxy-N-methyl-N-propyltryptamine, 5-methoxy-N,N-diethyltryptamine,5-methoxy-N-methyl-N-isopropyltryptamine,5-methoxy-N-ethyl-N-isopropyltryptamine,5-methoxy-N,N-diisopropyltryptamine, 5-methoxy-N,N-dipropyltryptamine,5-methoxy-N—N-dipropyltryptamine, 5-methoxy-N—N-diallyltryptamine,5-acetoxytryptamine, 5-acetoxy-N-methyltryptamine,5-acetoxy-N,N-dimethyltryptamine, 5-acetoxy-N-methyl-N-ethyltryptamine,5-methoxy-N-methyl-N-propyltryptamine, 5-acetoxy-N,N-diethyltryptamine,5-acetoxy-N-methyl-N-isopropyltryptamine,5-acetoxy-N-ethyl-N-isopropyltryptamine,5-acetoxy-N,N-diisopropyltryptamine, 5-acetoxy-N,N-dipropyltryptamine,5-acetoxy-N—N-dipropyltryptamine, 5-acetoxy-N—N-diallyltryptamine,α-methyltryptamine, N-ethyl-N-isopropyltryptamine,N-methyl-N-butyltryptamine, 2,α-dimethyltryptamine,α-N-dimethyltryptamine, α-methyl-N,N-dimethyltryptamine,α-ethyltryptamine, 2-methyl-N,N-dimethyltryptamine,2-methyl-N,N-diethyltryptamine, 1-methylpsilocin,5-methoxy-α-methyltryptamine, or a combination thereof.
 4. Thecomposition of claim 1, further comprising neurotropic or nootropicfungal or plant extracts, or other natural products, or purifiedcompounds thereof.
 5. The composition of claim 1, further comprising oneor more extracts or pure chemicals from other plant species comprisingBacopa species (Bacopa monnien), Gotu kola (Centella asiatica), andGingko (Gingko biloba), Ginger (Zingiber officinale), Holy Basil (Ocimumsanctum), Hu Zhang (Polygonum cuspidatum), Oregano (Origanum vulgare,Origanum onites), Rosemary (Rosmarinus officinalis, Rosmarinuseriocalyx, species in the genus Rosmarinus), Turmeric (Curcuma longa),Green Tea (Camellia sinensis), lavender (Lavandula spica and relatedspecies in the genus Lavandula), skullcap (Scutellaria lateriflora) oatstraw (Avena sativa, Avena byzantina), Salvia divinorum, aka Diviner'sSage, Banisteropsis caapi and Psychotria species, plants containingibogaine (Tabemanthe iboga, Voacanga africana and Tabemaemontanaundulate), peyote (Lophophora williamsii), the seeds of morning glory(Ipomoea tricolor and related species) and Hawaiian baby wood rose(Argyreia nervosa), Acacia confusa, Acacia obtusifolia, Acaciasimplicifolia, Desmanthus illinoensis, or Cannabis (Cannabis sativa, C.indica and C. ruderalis) or combinations thereof.
 6. The composition ofclaim 1, further comprising phenethylamines or amphetamines in pure formor extracts or isolates from plants comprising thereof.
 7. Thecomposition of claim 1, further comprising ketamine, pharmaceuticallyacceptable salts, hydrates, solvates, prodrugs, stereoisomers, ortautomers thereof.
 8. A composition comprising: an extract of Hericiumerinaceus; and niacin.
 9. The composition of claim 8, further comprisinga tryptamine, pharmaceutically acceptable salts, hydrates, or solvatesthereof.
 10. The composition of claim 9, wherein the tryptamine is4-hydroxytryptamine, 5-hydroxytryptamine (serotonin), aeruginascin,4-hydroxy-N,N,N-trimethyltryptamine, 5-hydroxy-N,N,N-trimethyltryptamine(bufotenidine), N-methyltryptamine, N-ethyltryptamine,N-methyl-N-ethyltryptamine, N-methyl-N-propyltryptamine,N,N-diethyltryptamine, N-methyl-N-isopropyltryptamine,N-ethyl-N-isopropyltryptamine, N,N-diisopropyltryptamine,N,N-dipropyltryptamine, N,N-diallyltryptamine, 4-hydroxytryptamine,4-hydroxy-N-methyltryptamine (norpsilocin),4-hydroxy-N-methyl-N-ethyltryptamine,4-hydroxy-N-methyl-N-propyltryptamine, 4-hydroxy-N,N-diethyltryptamine,4-hydroxy-N-ethyl-N-isopropyltryptamine,4-hydroxy-N,N-diisopropyltryptamine, 4-hydroxy-N,N-dipropyltryptamine,4-hydroxy-N,N-diallyltryptamine, 4-methoxytryptamine,4-methoxy-N-methyltryptamine (norpsilocin),4-methoxy-N-methyl-N-ethyltryptamine,4-methoxy-N-methyl-N-propyltryptamine, 4-methoxy-N,N-diethyltryptamine,4-methoxy-N-ethyl-N-isopropyltryptamine,4-methoxy-N,N-diisopropyltryptamine, 4-methoxy-N,N-dipropyltryptamine,4-methoxy-N—N-diallyltryptamine, 4-acetoxytryptamine,4-acetoxy-N-methyltryptamine, 4-acetoxy-N-methyl-N-ethyltryptamine,4-acetoxy-N-methyl-N-ethyltryptamine,4-acetoxy-N-methyl-N-propyltryptamine, 4-acetoxy-N,N-diethyltryptamine,4-acetoxy-N-methyl-N-isopropyltryptamine,4-acetoxy-N-ethyl-N-isopropyltryptamine,4-acetoxy-N,N-diisopropyltryptamine, 4-acetoxy-N—N-dipropyltryptamine,4-acetoxy-N—N-diallyltryptamine, 5-hydroxytryptamine,5-hydroxy-N-methyltryptamine, 5-hydroxy-N,N-dimethyltryptamine(bufotenine), 5-hydroxy-N-methyl-N-ethyltryptamine,5-hydroxy-N-methyl-N-propyltryptamine, 5-hydroxy-N,N-diethyltryptamine,5-hydroxy-N-methyl-N-isopropyltryptamine,5-hydroxy-N-ethyl-N-isopropyltryptamine,5-hydroxy-N,N-diisopropyltryptamine, 5-hydroxy-N,N-dipropyltryptamine,5-hydroxy-N—N-dipropyltryptamine, 5-hydroxy-N—N-diallyltryptamine,5-methoxytryptamine, 5-methoxy-N-methyltryptamine,5-methoxy-N,N-dimethyltryptamine, 5-methoxy-N-methyl-N-ethyltryptamine,5-methoxy-N-methyl-N-propyltryptamine, 5-methoxy-N,N-diethyltryptamine,5-methoxy-N-methyl-N-isopropyltryptamine,5-methoxy-N-ethyl-N-isopropyltryptamine,5-methoxy-N,N-diisopropyltryptamine, 5-methoxy-N,N-dipropyltryptamine,5-methoxy-N—N-dipropyltryptamine, 5-methoxy-N—N-diallyltryptamine,5-acetoxytryptamine, 5-acetoxy-N-methyltryptamine,5-acetoxy-N,N-dimethyltryptamine, 5-acetoxy-N-methyl-N-ethyltryptamine,5-methoxy-N-methyl-N-propyltryptamine, 5-acetoxy-N,N-diethyltryptamine,5-acetoxy-N-methyl-N-isopropyltryptamine,5-acetoxy-N-ethyl-N-isopropyltryptamine,5-acetoxy-N,N-diisopropyltryptamine, 5-acetoxy-N,N-dipropyltryptamine,5-acetoxy-N—N-dipropyltryptamine, 5-acetoxy-N—N-diallyltryptamine,α-methyltryptamine, N-ethyl-N-isopropyltryptamine,N-methyl-N-butyltryptamine, 2,α-dimethyltryptamine,α-N-dimethyltryptamine, α-methyl-N,N-dimethyltryptamine,α-ethyltryptamine, 2-methyl-N,N-dimethyltryptamine,2-methyl-N,N-diethyltryptamine, 1-methylpsilocin,5-methoxy-α-methyltryptamine, or a combination thereof.
 11. Thecomposition of claim 8, further comprising neurotropic or nootropicfungal or plant extracts, or other natural products, or purifiedcompounds thereof.
 12. The composition of claim 8, further comprisingone or more extracts or pure chemicals from other plant speciescomprising Bacopa species (Bacopa monnien), Gotu kola (Centellaasiatica), and Gingko (Gingko biloba), Ginger (Zingiber officinale),Holy Basil (Ocimum sanctum), Hu Zhang (Polygonum cuspidatum), Oregano(Origanum vulgare, Origanum onites), Rosemary (Rosmarinus officinalis,Rosmarinus eriocalyx, species in the genus Rosmarinus), Turmeric(Curcuma longa), Green Tea (Camellia sinensis), lavender (Lavandulaspica and related species in the genus Lavandula), skullcap (Scutellarialateriflora) oat straw (Avena sativa, Avena byzantina), Salviadivinorum, aka Diviner's Sage, Banisteropsis caapi and Psychotriaspecies, plants containing ibogaine (Tabemanthe iboga, Voacanga africanaand Tabemaemontana undulate), peyote (Lophophora williamsii), the seedsof morning glory (Ipomoea tricolor and related species) and Hawaiianbaby wood rose (Argyreia nervosa), Acacia confusa, Acacia obtusifolia,Acacia simplicifolia, Desmanthus illinoensis, or Cannabis (Cannabissativa, C. indica and C. ruderalis) or combinations thereof.
 13. Thecomposition of claim 8, further comprising phenethylamines oramphetamines in pure form or extracts or isolates from plants comprisingthereof.
 14. The composition of claim 8, further comprising ketamine,pharmaceutically acceptable salts, hydrates, solvates, prodrugs,stereoisomers, or tautomers thereof.
 15. A composition comprising: atryptamine, pharmaceutically acceptable salts, hydrates, or solvatesthereof; and niacin.
 16. The composition of claim 15, further comprisingan extract of Hericium erinaceus.
 17. The composition of claim 15,wherein the tryptamine is 4-hydroxytryptamine, 5-hydroxytryptamine(serotonin), aeruginascin, 4-hydroxy-N,N,N-trimethyltryptamine,5-hydroxy-N,N,N-trimethyltryptamine (bufotenidine), N-methyltryptamine,N-ethyltryptamine, N-methyl-N-ethyltryptamine,N-methyl-N-propyltryptamine, N,N-diethyltryptamine,N-methyl-N-isopropyltryptamine, N-ethyl-N-isopropyltryptamine,N,N-diisopropyltryptamine, N,N-dipropyltryptamine,N,N-diallyltryptamine, 4-hydroxytryptamine, 4-hydroxy-N-methyltryptamine(norpsilocin), 4-hydroxy-N-methyl-N-ethyltryptamine,4-hydroxy-N-methyl-N-propyltryptamine, 4-hydroxy-N,N-diethyltryptamine,4-hydroxy-N-ethyl-N-isopropyltryptamine,4-hydroxy-N,N-diisopropyltryptamine, 4-hydroxy-N,N-dipropyltryptamine,4-hydroxy-N,N-diallyltryptamine, 4-methoxytryptamine,4-methoxy-N-methyltryptamine (norpsilocin),4-methoxy-N-methyl-N-ethyltryptamine,4-methoxy-N-methyl-N-propyltryptamine, 4-methoxy-N,N-diethyltryptamine,4-methoxy-N-ethyl-N-isopropyltryptamine,4-methoxy-N,N-diisopropyltryptamine, 4-methoxy-N,N-dipropyltryptamine,4-methoxy-N—N-diallyltryptamine, 4-acetoxytryptamine,4-acetoxy-N-methyltryptamine, 4-acetoxy-N-methyl-N-ethyltryptamine,4-acetoxy-N-methyl-N-ethyltryptamine,4-acetoxy-N-methyl-N-propyltryptamine, 4-acetoxy-N,N-diethyltryptamine,4-acetoxy-N-methyl-N-isopropyltryptamine,4-acetoxy-N-ethyl-N-isopropyltryptamine,4-acetoxy-N,N-diisopropyltryptamine, 4-acetoxy-N—N-dipropyltryptamine,4-acetoxy-N—N-diallyltryptamine, 5-hydroxytryptamine,5-hydroxy-N-methyltryptamine, 5-hydroxy-N,N-dimethyltryptamine(bufotenine), 5-hydroxy-N-methyl-N-ethyltryptamine,5-hydroxy-N-methyl-N-propyltryptamine, 5-hydroxy-N,N-diethyltryptamine,5-hydroxy-N-methyl-N-isopropyltryptamine,5-hydroxy-N-ethyl-N-isopropyltryptamine,5-hydroxy-N,N-diisopropyltryptamine, 5-hydroxy-N,N-dipropyltryptamine,5-hydroxy-N—N-dipropyltryptamine, 5-hydroxy-N—N-diallyltryptamine,5-methoxytryptamine, 5-methoxy-N-methyltryptamine,5-methoxy-N,N-dimethyltryptamine, 5-methoxy-N-methyl-N-ethyltryptamine,5-methoxy-N-methyl-N-propyltryptamine, 5-methoxy-N,N-diethyltryptamine,5-methoxy-N-methyl-N-isopropyltryptamine,5-methoxy-N-ethyl-N-isopropyltryptamine,5-methoxy-N,N-diisopropyltryptamine, 5-methoxy-N,N-dipropyltryptamine,5-methoxy-N—N-dipropyltryptamine, 5-methoxy-N—N-diallyltryptamine,5-acetoxytryptamine, 5-acetoxy-N-methyltryptamine,5-acetoxy-N,N-dimethyltryptamine, 5-acetoxy-N-methyl-N-ethyltryptamine,5-methoxy-N-methyl-N-propyltryptamine, 5-acetoxy-N,N-diethyltryptamine,5-acetoxy-N-methyl-N-isopropyltryptamine,5-acetoxy-N-ethyl-N-isopropyltryptamine,5-acetoxy-N,N-diisopropyltryptamine, 5-acetoxy-N,N-dipropyltryptamine,5-acetoxy-N—N-dipropyltryptamine, 5-acetoxy-N—N-diallyltryptamine,α-methyltryptamine, N-ethyl-N-isopropyltryptamine,N-methyl-N-butyltryptamine, 2,α-dimethyltryptamine,α-N-dimethyltryptamine, α-methyl-N,N-dimethyltryptamine,α-ethyltryptamine, 2-methyl-N,N-dimethyltryptamine,2-methyl-N,N-diethyltryptamine, 1-methylpsilocin,5-methoxy-α-methyltryptamine, or a combination thereof.
 18. Thecomposition of claim 15, further comprising neurotropic or nootropicfungal or plant extracts, or other natural products, or purifiedcompounds thereof.
 19. The composition of claim 15, further comprisingone or more extracts or pure chemicals from other plant speciescomprising Bacopa species (Bacopa monnien), Gotu kola (Centellaasiatica), and Gingko (Gingko biloba), Ginger (Zingiber officinale),Holy Basil (Ocimum sanctum), Hu Zhang (Polygonum cuspidatum), Oregano(Origanum vulgare, Origanum onites), Rosemary (Rosmarinus officinalis,Rosmarinus eriocalyx, species in the genus Rosmarinus), Turmeric(Curcuma longa), Green Tea (Camellia sinensis), lavender (Lavandulaspica and related species in the genus Lavandula), skullcap (Scutellarialateriflora) oat straw (Avena sativa, Avena byzantina), Salviadivinorum, aka Diviner's Sage, Banisteropsis caapi and Psychotriaspecies, plants containing ibogaine (Tabemanthe iboga, Voacanga africanaand Tabemaemontana undulate), peyote (Lophophora williamsii), the seedsof morning glory (Ipomoea tricolor and related species) and Hawaiianbaby wood rose (Argyreia nervosa), Acacia confusa, Acacia obtusifolia,Acacia simplicifolia, Desmanthus illinoensis, or Cannabis (Cannabissativa, C. indica and C. ruderalis) or combinations thereof.
 20. Thecomposition of claim 15, further comprising phenethylamines oramphetamines in pure form or extracts or isolates from plants comprisingthereof.
 21. The composition of claim 15, further comprising ketamine,pharmaceutically acceptable salts, hydrates, solvates, prodrugs,stereoisomers, or tautomers thereof.
 22. A method of treating orpreventing serotonin (5-hydroxytryptamine, 5-HT) receptor disorders,neuronal injuries, neurodegeneration, neurological diseases, congenitalor organic cognitive impairment, learning disabilities, autism spectrumdisorder, psychiatric and mood disorders, cognitive enhancement,physical or motor neuron enhancement, or general improvement of mentalhealth in a subject in need thereof, the method comprising administeringto the subject a therapeutically effective amount of a compositioncomprising: a tryptamine, pharmaceutically acceptable salts, hydrates,or solvates thereof; and an extract of Hericium erinaceus.
 23. Thecomposition of claim 22, further comprising niacin.
 24. A method oftreating or preventing serotonin (5-hydroxytryptamine, 5-HT) receptordisorders, neuronal injuries, neurodegeneration, neurological diseases,congenital or organic cognitive impairment, learning disabilities,autism spectrum disorder, psychiatric and mood disorders, cognitiveenhancement, physical or motor neuron enhancement, or generalimprovement of mental health in a subject in need thereof, the methodcomprising administering to the subject a therapeutically effectiveamount of a composition comprising: an extract of Hericium erinaceus;and niacin.
 25. The composition of claim 24, further comprising atryptamine, pharmaceutically acceptable salts, hydrates, or solvatesthereof.
 26. A method of treating or preventing serotonin(5-hydroxytryptamine, 5-HT) receptor disorders, neuronal injuries,neurodegeneration, neurological diseases, congenital or organiccognitive impairment, learning disabilities, autism spectrum disorder,psychiatric and mood disorders, cognitive enhancement, physical or motorneuron enhancement, or general improvement of mental health in a subjectin need thereof, the method comprising administering to the subject atherapeutically effective amount of a composition comprising: atryptamine, pharmaceutically acceptable salts, hydrates, or solvatesthereof; and niacin.
 27. The composition of claim 26, further comprisingan extract of Hericium erinaceus.